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排序方式: 共有641条查询结果,搜索用时 15 毫秒
561.
Peacock CS Seeger K Harris D Murphy L Ruiz JC Quail MA Peters N Adlem E Tivey A Aslett M Kerhornou A Ivens A Fraser A Rajandream MA Carver T Norbertczak H Chillingworth T Hance Z Jagels K Moule S Ormond D Rutter S Squares R Whitehead S Rabbinowitsch E Arrowsmith C White B Thurston S Bringaud F Baldauf SL Faulconbridge A Jeffares D Depledge DP Oyola SO Hilley JD Brito LO Tosi LR Barrell B Cruz AK Mottram JC Smith DF Berriman M 《Nature genetics》2007,39(7):839-847
Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only approximately 200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader-associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage. 相似文献
562.
Crow YJ Leitch A Hayward BE Garner A Parmar R Griffith E Ali M Semple C Aicardi J Babul-Hirji R Baumann C Baxter P Bertini E Chandler KE Chitayat D Cau D Déry C Fazzi E Goizet C King MD Klepper J Lacombe D Lanzi G Lyall H Martínez-Frías ML Mathieu M McKeown C Monier A Oade Y Quarrell OW Rittey CD Rogers RC Sanchis A Stephenson JB Tacke U Till M Tolmie JL Tomlin P Voit T Weschke B Woods CG Lebon P Bonthron DT Ponting CP Jackson AP 《Nature genetics》2006,38(8):910-916
Aicardi-Goutières syndrome (AGS) is an autosomal recessive neurological disorder, the clinical and immunological features of which parallel those of congenital viral infection. Here we define the composition of the human ribonuclease H2 enzyme complex and show that AGS can result from mutations in the genes encoding any one of its three subunits. Our findings demonstrate a role for ribonuclease H in human neurological disease and suggest an unanticipated relationship between ribonuclease H2 and the antiviral immune response that warrants further investigation. 相似文献
563.
Rivière JB van Bon BW Hoischen A Kholmanskikh SS O'Roak BJ Gilissen C Gijsen S Sullivan CT Christian SL Abdul-Rahman OA Atkin JF Chassaing N Drouin-Garraud V Fry AE Fryns JP Gripp KW Kempers M Kleefstra T Mancini GM Nowaczyk MJ van Ravenswaaij-Arts CM Roscioli T Marble M Rosenfeld JA Siu VM de Vries BB Shendure J Verloes A Veltman JA Brunner HG Ross ME Pilz DT Dobyns WB 《Nature genetics》2012,44(4):440-4, S1-2
Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes. 相似文献
564.
Jacobs KB Yeager M Zhou W Wacholder S Wang Z Rodriguez-Santiago B Hutchinson A Deng X Liu C Horner MJ Cullen M Epstein CG Burdett L Dean MC Chatterjee N Sampson J Chung CC Kovaks J Gapstur SM Stevens VL Teras LT Gaudet MM Albanes D Weinstein SJ Virtamo J Taylor PR Freedman ND Abnet CC Goldstein AM Hu N Yu K Yuan JM Liao L Ding T Qiao YL Gao YT Koh WP Xiang YB Tang ZZ Fan JH Aldrich MC Amos C Blot WJ Bock CH Gillanders EM Harris CC Haiman CA Henderson BE Kolonel LN Le Marchand L McNeill LH 《Nature genetics》2012,44(6):651-658
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases. 相似文献
565.
Wen W Cho YS Zheng W Dorajoo R Kato N Qi L Chen CH Delahanty RJ Okada Y Tabara Y Gu D Zhu D Haiman CA Mo Z Gao YT Saw SM Go MJ Takeuchi F Chang LC Kokubo Y Liang J Hao M Le Marchand L Zhang Y Hu Y Wong TY Long J Han BG Kubo M Yamamoto K Su MH Miki T Henderson BE Song H Tan A He J Ng DP Cai Q Tsunoda T Tsai FJ Iwai N Chen GK Shi J Xu J Sim X Xiang YB Maeda S Ong RT Li C Nakamura Y Aung T Kamatani N Liu JJ Lu W Yokota M Seielstad M 《Nature genetics》2012,44(3):307-311
Multiple genetic loci associated with obesity or body mass index (BMI) have been identified through genome-wide association studies conducted predominantly in populations of European ancestry. We performed a meta-analysis of associations between BMI and approximately 2.4 million SNPs in 27,715 east Asians, which was followed by in silico and de novo replication studies in 37,691 and 17,642 additional east Asians, respectively. We identified ten BMI-associated loci at genome-wide significance (P < 5.0 × 10(-8)), including seven previously identified loci (FTO, SEC16B, MC4R, GIPR-QPCTL, ADCY3-DNAJC27, BDNF and MAP2K5) and three novel loci in or near the CDKAL1, PCSK1 and GP2 genes. Three additional loci nearly reached the genome-wide significance threshold, including two previously identified loci in the GNPDA2 and TFAP2B genes and a newly identified signal near PAX6, all of which were associated with BMI with P < 5.0 × 10(-7). Findings from this study may shed light on new pathways involved in obesity and demonstrate the value of conducting genetic studies in non-European populations. 相似文献
566.
Frédéric?Delolme Cyril?Anastasi Lindsay?B.?Alcaraz Valentin?Mendoza Sandrine?Vadon-Le Goff Maya?Talantikite Robin?Capomaccio Jimmy?Mevaere La?titia?Fortin Dominique?Mazzocut Odile?Damour Isabelle?Zanella-Cléon David?J.?S.?Hulmes Christopher?M.?Overall Ulrich?Valcourt Fernando?Lopez-Casillas Catherine?MoaliEmail author 《Cellular and molecular life sciences : CMLS》2015,72(5):1009-1027
The metalloproteinase BMP-1 (bone morphogenetic protein-1) plays a major role in the control of extracellular matrix (ECM) assembly and growth factor activation. Most of the growth factors activated by BMP-1 are members of the TGF-β superfamily known to regulate multiple biological processes including embryonic development, wound healing, inflammation and tumor progression. In this study, we used an iTRAQ (isobaric tags for relative and absolute quantification)-based quantitative proteomic approach to reveal the release of proteolytic fragments from the cell surface or the ECM by BMP-1. Thirty-eight extracellular proteins were found in significantly higher or lower amounts in the conditioned medium of HT1080 cells overexpressing BMP-1 and thus, could be considered as candidate substrates. Strikingly, three of these new candidates (betaglycan, CD109 and neuropilin-1) were TGF-β co-receptors, also acting as antagonists when released from the cell surface, and were chosen for further substrate validation. Betaglycan and CD109 proved to be directly cleaved by BMP-1 and the corresponding cleavage sites were extensively characterized using a new mass spectrometry approach. Furthermore, we could show that the ability of betaglycan and CD109 to interact with TGF-β was altered after cleavage by BMP-1, leading to increased and prolonged SMAD2 phosphorylation in BMP-1-overexpressing cells. Betaglycan processing was also observed in primary corneal keratocytes, indicating a general and novel mechanism by which BMP-1 directly affects signaling by controlling TGF-β co-receptor activity. The proteomic data have been submitted to ProteomeXchange with the identifier PXD000786 and doi: 10.6019/PXD000786. 相似文献
567.
Iain R. Murray Christopher C. West Winters R. Hardy Aaron W. James Tea Soon Park Alan Nguyen Tulyapruek Tawonsawatruk Lorenza Lazzari Chia Soo Bruno Péault 《Cellular and molecular life sciences : CMLS》2014,71(8):1353-1374
Mesenchymal stem/stromal cells (MSCs) can regenerate tissues by direct differentiation or indirectly by stimulating angiogenesis, limiting inflammation, and recruiting tissue-specific progenitor cells. MSCs emerge and multiply in long-term cultures of total cells from the bone marrow or multiple other organs. Such a derivation in vitro is simple and convenient, hence popular, but has long precluded understanding of the native identity, tissue distribution, frequency, and natural role of MSCs, which have been defined and validated exclusively in terms of surface marker expression and developmental potential in culture into bone, cartilage, and fat. Such simple, widely accepted criteria uniformly typify MSCs, even though some differences in potential exist, depending on tissue sources. Combined immunohistochemistry, flow cytometry, and cell culture have allowed tracking the artifactual cultured mesenchymal stem/stromal cells back to perivascular anatomical regions. Presently, both pericytes enveloping microvessels and adventitial cells surrounding larger arteries and veins have been described as possible MSC forerunners. While such a vascular association would explain why MSCs have been isolated from virtually all tissues tested, the origin of the MSCs grown from umbilical cord blood remains unknown. In fact, most aspects of the biology of perivascular MSCs are still obscure, from the emergence of these cells in the embryo to the molecular control of their activity in adult tissues. Such dark areas have not compromised intents to use these cells in clinical settings though, in which purified perivascular cells already exhibit decisive advantages over conventional MSCs, including purity, thorough characterization and, principally, total independence from in vitro culture. A growing body of experimental data is currently paving the way to the medical usage of autologous sorted perivascular cells for indications in which MSCs have been previously contemplated or actually used, such as bone regeneration and cardiovascular tissue repair. 相似文献
568.
Soler Artigas M Loth DW Wain LV Gharib SA Obeidat M Tang W Zhai G Zhao JH Smith AV Huffman JE Albrecht E Jackson CM Evans DM Cadby G Fornage M Manichaikul A Lopez LM Johnson T Aldrich MC Aspelund T Barroso I Campbell H Cassano PA Couper DJ Eiriksdottir G Franceschini N Garcia M Gieger C Gislason GK Grkovic I Hammond CJ Hancock DB Harris TB Ramasamy A Heckbert SR Heliövaara M Homuth G Hysi PG James AL Jankovic S Joubert BR Karrasch S Klopp N Koch B Kritchevsky SB Launer LJ Liu Y Loehr LR 《Nature genetics》2011,43(11):1082-1090
Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function. 相似文献
569.
Adrianto I Wen F Templeton A Wiley G King JB Lessard CJ Bates JS Hu Y Kelly JA Kaufman KM Guthridge JM Alarcón-Riquelme ME;BIOLUPUS GENLES Networks Anaya JM Bae SC Bang SY Boackle SA Brown EE Petri MA Gallant C Ramsey-Goldman R Reveille JD Vila LM Criswell LA Edberg JC Freedman BI Gregersen PK Gilkeson GS Jacob CO James JA Kamen DL Kimberly RP Martin J Merrill JT Niewold TB Park SY Pons-Estel BA Scofield RH Stevens AM Tsao BP Vyse TJ Langefeld CD Harley JB Moser KL Webb CF Humphrey MB 《Nature genetics》2011,43(3):253-258
Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 × 10(-8), odds ratio = 1.70) and Korean (P = 8.33 × 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-κB subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE. 相似文献
570.
Lindström S Vachon CM Li J Varghese J Thompson D Warren R Brown J Leyland J Audley T Wareham NJ Loos RJ Paterson AD Rommens J Waggott D Martin LJ Scott CG Pankratz VS Hankinson SE Hazra A Hunter DJ Hopper JL Southey MC Chanock SJ Silva Idos S Liu J Eriksson L Couch FJ Stone J Apicella C Czene K Kraft P Hall P Easton DF Boyd NF Tamimi RM 《Nature genetics》2011,43(3):185-187
High-percent mammographic density adjusted for age and body mass index is one of the strongest risk factors for breast cancer. We conducted a meta analysis of five genome-wide association studies of percent mammographic density and report an association with rs10995190 in ZNF365 (combined P = 9.6 × 10(-10)). Common variants in ZNF365 have also recently been associated with susceptibility to breast cancer. 相似文献