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561.
Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. 总被引:29,自引:0,他引:29
M D Katinka S Duprat E Cornillot G Méténier F Thomarat G Prensier V Barbe E Peyretaillade P Brottier P Wincker F Delbac H El Alaoui P Peyret W Saurin M Gouy J Weissenbach C P Vivarès 《Nature》2001,414(6862):450-453
Microsporidia are obligate intracellular parasites infesting many animal groups. Lacking mitochondria and peroxysomes, these unicellular eukaryotes were first considered a deeply branching protist lineage that diverged before the endosymbiotic event that led to mitochondria. The discovery of a gene for a mitochondrial-type chaperone combined with molecular phylogenetic data later implied that microsporidia are atypical fungi that lost mitochondria during evolution. Here we report the DNA sequences of the 11 chromosomes of the approximately 2.9-megabase (Mb) genome of Encephalitozoon cuniculi (1,997 potential protein-coding genes). Genome compaction is reflected by reduced intergenic spacers and by the shortness of most putative proteins relative to their eukaryote orthologues. The strong host dependence is illustrated by the lack of genes for some biosynthetic pathways and for the tricarboxylic acid cycle. Phylogenetic analysis lends substantial credit to the fungal affiliation of microsporidia. Because the E. cuniculi genome contains genes related to some mitochondrial functions (for example, Fe-S cluster assembly), we hypothesize that microsporidia have retained a mitochondrion-derived organelle. 相似文献
562.
Over the last ten years there has been growing acceptance that retinal photoreception among mammals extends beyond rods and
cones to include a small number of intrinsically photosensitive retinal ganglion cells (ipRGCs). These ipRGCs are capable
of responding to light in the absence of rod/cone input thanks to expression of an opsin photopigment called melanopsin. They
are specialised for measuring ambient levels of light (irradiance) for a wide variety of so-called non-image-forming light
responses. These include synchronisation of circadian clocks to light:dark cycles and the regulation of pupil size, sleep
propensity and pineal melatonin production. Here, we provide a review of some of the landmark discoveries in this fast developing
field, paying particular emphasis to recent findings and key areas for future investigation. 相似文献
563.
Smallpox virus eradication was one of the greatest successes of the 20th century. Moreover, the quest to combat its use in biological warfare, has fueled efforts to understand residual immune memory and to develop new animal models by the scientific community. Although the literature is full of animal studies of vaccinia virus infection, continuing efforts have helped to increase our knowledge regarding humoral and cellular memory to non-persistent pathogens and to study factors that might influence further vaccination strategies in humans. In addition, the potent immunostimulatory action of poxvirus vectors has led to development and evaluation of new-generation vaccine candidates, which will be discussed in this review. 相似文献
564.
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
565.
Verónica Parrillas Laura Martínez-Muñoz Borja L. Holgado Amit Kumar Graciela Cascio Pilar Lucas José Miguel Rodríguez-Frade Marcos Malumbres Ana C. Carrera Karel HM van Wely Mario Mellado 《Cellular and molecular life sciences : CMLS》2013,70(3):545-558
Hypermethylation of SOCS genes is associated with many human cancers, suggesting a role as tumor suppressors. As adaptor molecules for ubiquitin ligases, SOCS proteins modulate turnover of numerous target proteins. Few SOCS targets identified so far have a direct role in cell cycle progression; the mechanism by which SOCS regulate the cell cycle thus remains largely unknown. Here we show that SOCS1 overexpression inhibits in vitro and in vivo expansion of human melanoma cells, and that SOCS1 associates specifically with Cdh1, triggering its degradation by the proteasome. Cells therefore show a G1/S transition defect, as well as a secondary blockade in mitosis and accumulation of cells in metaphase. SOCS1 expression correlated with a reduction in cyclin D/E levels and an increase in the tumor suppressor p19, as well as the CDK inhibitor p53, explaining the G1/S transition defect. As a result of Cdh1 degradation, SOCS1-expressing cells accumulated cyclin B1 and securin, as well as apparently inactive Cdc20, in mitosis. Levels of the late mitotic Cdh1 substrate Aurora A did not change. These observations comprise a hitherto unreported mechanism of SOCS1 tumor suppression, suggesting this molecule as a candidate for the design of new therapeutic strategies for human melanoma. 相似文献
566.
Liana Ghazarian Julien Diana Yannick Simoni Lucie Beaudoin Agnès Lehuen 《Cellular and molecular life sciences : CMLS》2013,70(2):239-255
Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells. Even though extensive scientific research has yielded important insights into the immune mechanisms involved in pancreatic β-cell destruction, little is known about the events that trigger the autoimmune process. Recent epidemiological and experimental data suggest that environmental factors are involved in this process. In this review, we discuss the role of viruses as an environmental factor on the development of type 1 diabetes, and the immune mechanisms by which they can trigger or protect against this pathology. 相似文献
567.
KLHL3 mutations cause familial hyperkalemic hypertension by impairing ion transport in the distal nephron 总被引:1,自引:0,他引:1
Louis-Dit-Picard H Barc J Trujillano D Miserey-Lenkei S Bouatia-Naji N Pylypenko O Beaurain G Bonnefond A Sand O Simian C Vidal-Petiot E Soukaseum C Mandet C Broux F Chabre O Delahousse M Esnault V Fiquet B Houillier P Bagnis CI Koenig J Konrad M Landais P Mourani C Niaudet P Probst V Thauvin C Unwin RJ Soroka SD Ehret G Ossowski S Caulfield M;International Consortium for Blood Pressure 《Nature genetics》2012,44(4):456-60, S1-3
Familial hyperkalemic hypertension (FHHt) is a Mendelian form of arterial hypertension that is partially explained by mutations in WNK1 and WNK4 that lead to increased activity of the Na(+)-Cl(-) cotransporter (NCC) in the distal nephron. Using combined linkage analysis and whole-exome sequencing in two families, we identified KLHL3 as a third gene responsible for FHHt. Direct sequencing of 43 other affected individuals revealed 11 additional missense mutations that were associated with heterogeneous phenotypes and diverse modes of inheritance. Polymorphisms at KLHL3 were not associated with blood pressure. The KLHL3 protein belongs to the BTB-BACK-kelch family of actin-binding proteins that recruit substrates for Cullin3-based ubiquitin ligase complexes. KLHL3 is coexpressed with NCC and downregulates NCC expression at the cell surface. Our study establishes a role for KLHL3 as a new member of the complex signaling pathway regulating ion homeostasis in the distal nephron and indirectly blood pressure. 相似文献
568.
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
569.
Freilinger T Anttila V de Vries B Malik R Kallela M Terwindt GM Pozo-Rosich P Winsvold B Nyholt DR van Oosterhout WP Artto V Todt U Hämäläinen E Fernández-Morales J Louter MA Kaunisto MA Schoenen J Raitakari O Lehtimäki T Vila-Pueyo M Göbel H Wichmann E Sintas C Uitterlinden AG Hofman A Rivadeneira F Heinze A Tronvik E van Duijn CM Kaprio J Cormand B Wessman M Frants RR Meitinger T Müller-Myhsok B Zwart JA Färkkilä M Macaya A Ferrari MD Kubisch C Palotie A Dichgans M 《Nature genetics》2012,44(7):777-782
Migraine without aura is the most common form of migraine, characterized by recurrent disabling headache and associated autonomic symptoms. To identify common genetic variants associated with this migraine type, we analyzed genome-wide association data of 2,326 clinic-based German and Dutch individuals with migraine without aura and 4,580 population-matched controls. We selected SNPs from 12 loci with 2 or more SNPs associated with P values of <1 × 10(-5) for replication testing in 2,508 individuals with migraine without aura and 2,652 controls. SNPs at two of these loci showed convincing replication: at 1q22 (in MEF2D; replication P = 4.9 × 10(-4); combined P = 7.06 × 10(-11)) and at 3p24 (near TGFBR2; replication P = 1.0 × 10(-4); combined P = 1.17 × 10(-9)). In addition, SNPs at the PHACTR1 and ASTN2 loci showed suggestive evidence of replication (P = 0.01; combined P = 3.20 × 10(-8) and P = 0.02; combined P = 3.86 × 10(-8), respectively). We also replicated associations at two previously reported migraine loci in or near TRPM8 and LRP1. This study identifies the first susceptibility loci for migraine without aura, thereby expanding our knowledge of this debilitating neurological disorder. 相似文献
570.
Corbicula fluminea is well known as an invasive filter-feeding freshwater bivalve with a variety of effects on ecosystem processes. However, C. fluminea has been relatively unstudied in the rivers of the western United States. In June 2003, we sampled C. fluminea at 16 sites in the San Joaquin River watershed of California, which was invaded by C. fluminea in the 1940s. Corbicula fluminea was common in 2 tributaries to the San Joaquin River, reaching densities of 200 clams ? m –2 , but was rare in the San Joaquin River. Biomass followed a similar pattern. Clams of the same age were shorter in the San Joaquin River than in the tributaries. Distribution of clams was different in the 2 tributaries, but the causes of the difference are unknown. The low density and biomass of clams in the San Joaquin River was likely due to stressful habitat or to water quality, because food was abundant. The success of C. fluminea invasions and subsequent effects on trophic processes likely depends on multiple factors. As C. fluminea continues to expand its range around the world, questions regarding invasion success and effects on ecosystems will become important in a wide array of environmental settings. 相似文献