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排序方式: 共有288条查询结果,搜索用时 125 毫秒
211.
212.
Briggs TA Rice GI Daly S Urquhart J Gornall H Bader-Meunier B Baskar K Baskar S Baudouin V Beresford MW Black GC Dearman RJ de Zegher F Foster ES Francès C Hayman AR Hilton E Job-Deslandre C Kulkarni ML Le Merrer M Linglart A Lovell SC Maurer K Musset L Navarro V Picard C Puel A Rieux-Laucat F Roifman CM Scholl-Bürgi S Smith N Szynkiewicz M Wiedeman A Wouters C Zeef LA Casanova JL Elkon KB Janckila A Lebon P Crow YJ 《Nature genetics》2011,43(2):127-131
We studied ten individuals from eight families showing features consistent with the immuno-osseous dysplasia spondyloenchondrodysplasia. Of particular note was the diverse spectrum of autoimmune phenotypes observed in these individuals (cases), including systemic lupus erythematosus, Sj?gren's syndrome, hemolytic anemia, thrombocytopenia, hypothyroidism, inflammatory myositis, Raynaud's disease and vitiligo. Haplotype data indicated the disease gene to be on chromosome 19p13, and linkage analysis yielded a combined multipoint log(10) odds (LOD) score of 3.6. Sequencing of ACP5, encoding tartrate-resistant acid phosphatase, identified biallelic mutations in each of the cases studied, and in vivo testing confirmed a loss of expressed protein. All eight cases assayed showed elevated serum interferon alpha activity, and gene expression profiling in whole blood defined a type I interferon signature. Our findings reveal a previously unrecognized link between tartrate-resistant acid phosphatase activity and interferon metabolism and highlight the importance of type I interferon in the genesis of autoimmunity. 相似文献
213.
The genome of Theobroma cacao 总被引:2,自引:0,他引:2
Argout X Salse J Aury JM Guiltinan MJ Droc G Gouzy J Allegre M Chaparro C Legavre T Maximova SN Abrouk M Murat F Fouet O Poulain J Ruiz M Roguet Y Rodier-Goud M Barbosa-Neto JF Sabot F Kudrna D Ammiraju JS Schuster SC Carlson JE Sallet E Schiex T Dievart A Kramer M Gelley L Shi Z Bérard A Viot C Boccara M Risterucci AM Guignon V Sabau X Axtell MJ Ma Z Zhang Y Brown S Bourge M Golser W Song X Clement D Rivallan R Tahi M Akaza JM Pitollat B Gramacho K D'Hont A Brunel D Infante D Kebe I Costet P 《Nature genetics》2011,43(2):101-108
We sequenced and assembled the draft genome of Theobroma cacao, an economically important tropical-fruit tree crop that is the source of chocolate. This assembly corresponds to 76% of the estimated genome size and contains almost all previously described genes, with 82% of these genes anchored on the 10 T. cacao chromosomes. Analysis of this sequence information highlighted specific expansion of some gene families during evolution, for example, flavonoid-related genes. It also provides a major source of candidate genes for T. cacao improvement. Based on the inferred paleohistory of the T. cacao genome, we propose an evolutionary scenario whereby the ten T. cacao chromosomes were shaped from an ancestor through eleven chromosome fusions. 相似文献
214.
215.
Götz J Eckert A Matamales M Ittner LM Liu X 《Cellular and molecular life sciences : CMLS》2011,68(20):3359-3375
Alzheimer's disease (AD) is reaching epidemic proportions, yet a cure is not yet available. While the genetic causes of the rare familial inherited forms of AD are understood, the causes of the sporadic forms of the disease are not. Histopathologically, these two forms of AD are indistinguishable: they are characterized by amyloid-β (Aβ) peptide-containing amyloid plaques and tau-containing neurofibrillary tangles. In this review we compare AD to frontotemporal dementia (FTD), a subset of which is characterized by tau deposition in the absence of overt plaques. A host of transgenic animal AD models have been established through the expression of human proteins with pathogenic mutations previously identified in familial AD and FTD. Determining how these mutant proteins cause disease in vivo should contribute to an understanding of the causes of the more frequent sporadic forms. We discuss the insight transgenic animal models have provided into Aβ and tau toxicity, also with regards to mitochondrial function and the crucial role tau plays in mediating Aβ toxicity. We also discuss the role of miRNAs in mediating the toxic effects of the Aβ peptide. 相似文献
216.
Konstanze Zieger Juliane Weiner Anne Kunath Martin Gericke Kerstin Krause Matthias Kern Michael Stumvoll Nora Klöting Matthias Blüher John T. Heiker 《Cellular and molecular life sciences : CMLS》2018,75(4):727-742
Vaspin is an adipokine which improves glucose metabolism and insulin sensitivity in obesity. Kallikrein 7 (KLK7) is the first known protease target inhibited by vaspin and a potential target for the treatment of metabolic disorders. Here, we tested the hypothesis that inhibition of KLK7 in adipose tissue may beneficially affect glucose metabolism and adipose tissue function. Therefore, we have inactivated the Klk7 gene in adipose tissue using conditional gene-targeting strategies in mice. Klk7-deficient mice (ATKlk7 ?/?) exhibited less weight gain, predominant expansion of subcutaneous adipose tissue and improved whole body insulin sensitivity under a high fat diet (HFD). ATKlk7 ?/? mice displayed higher energy expenditure and food intake, most likely due to altered adipokine secretion including lower circulating leptin. Pro-inflammatory cytokine expression was significantly reduced in combination with an increased percentage of alternatively activated (anti-inflammatory) M2 macrophages in epigonadal adipose tissue of ATKlk7 ?/?. Taken together, by attenuating adipose tissue inflammation, altering adipokine secretion and epigonadal adipose tissue expansion, Klk7 deficiency in adipose tissue partially ameliorates the adverse effects of HFD-induced obesity. In summary, we provide first evidence for a previously unrecognized role of KLK7 in adipose tissue with effects on whole body energy expenditure and insulin sensitivity. 相似文献
217.
218.
Marina El Haddad Cécile Notarnicola Brendan Evano Nour El Khatib Marine Blaquière Anne Bonnieu Shahragim Tajbakhsh Gérald Hugon Barbara Vernus Jacques Mercier Gilles Carnac 《Cellular and molecular life sciences : CMLS》2017,74(10):1923-1936
Muscle satellite cells are resistant to cytotoxic agents, and they express several genes that confer resistance to stress, thus allowing efficient dystrophic muscle regeneration after transplantation. However, once they are activated, this capacity to resist to aggressive agents is diminished resulting in massive death of transplanted cells. Although cell immaturity represents a survival advantage, the signalling pathways involved in the control of the immature state remain to be explored. Here, we show that incubation of human myoblasts with retinoic acid impairs skeletal muscle differentiation through activation of the retinoic-acid receptor family of nuclear receptor. Conversely, pharmacologic or genetic inactivation of endogenous retinoic-acid receptors improved myoblast differentiation. Retinoic acid inhibits the expression of early and late muscle differentiation markers and enhances the expression of myogenic specification genes, such as PAX7 and PAX3. These results suggest that the retinoic-acid-signalling pathway might maintain myoblasts in an undifferentiated/immature stage. To determine the relevance of these observations, we characterised the retinoic-acid-signalling pathways in freshly isolated satellite cells in mice and in siMYOD immature human myoblasts. Our analysis reveals that the immature state of muscle progenitors is correlated with high expression of several genes of the retinoic-acid-signalling pathway both in mice and in human. Taken together, our data provide evidences for an important role of the retinoic-acid-signalling pathway in the regulation of the immature state of muscle progenitors. 相似文献
219.
Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome 总被引:1,自引:0,他引:1
Koolen DA Kramer JM Neveling K Nillesen WM Moore-Barton HL Elmslie FV Toutain A Amiel J Malan V Tsai AC Cheung SW Gilissen C Verwiel ET Martens S Feuth T Bongers EM de Vries P Scheffer H Vissers LE de Brouwer AP Brunner HG Veltman JA Schenck A Yntema HG de Vries BB 《Nature genetics》2012,44(6):639-641
We show that haploinsufficiency of KANSL1 is sufficient to cause the 17q21.31 microdeletion syndrome, a multisystem disorder characterized by intellectual disability, hypotonia and distinctive facial features. The KANSL1 protein is an evolutionarily conserved regulator of the chromatin modifier KAT8, which influences gene expression through histone H4 lysine 16 (H4K16) acetylation. RNA sequencing studies in cell lines derived from affected individuals and the presence of learning deficits in Drosophila melanogaster mutants suggest a role for KANSL1 in neuronal processes. 相似文献
220.
Genetic Analysis of Psoriasis Consortium & the Wellcome Trust Case Control Consortium Strange A Capon F Spencer CC Knight J Weale ME Allen MH Barton A Band G Bellenguez C Bergboer JG Blackwell JM Bramon E Bumpstead SJ Casas JP Cork MJ Corvin A Deloukas P Dilthey A Duncanson A Edkins S Estivill X Fitzgerald O Freeman C Giardina E Gray E Hofer A Hüffmeier U Hunt SE Irvine AD Jankowski J Kirby B Langford C Lascorz J Leman J Leslie S Mallbris L Markus HS Mathew CG McLean WH McManus R 《Nature genetics》2010,42(11):985-990
To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 × 10?? and two loci with a combined P < 5 × 10??). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 × 10??). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis. 相似文献