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排序方式: 共有238条查询结果,搜索用时 15 毫秒
61.
A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region 总被引:1,自引:0,他引:1
Smyth DJ Cooper JD Bailey R Field S Burren O Smink LJ Guja C Ionescu-Tirgoviste C Widmer B Dunger DB Savage DA Walker NM Clayton DG Todd JA 《Nature genetics》2006,38(6):617-619
In this study we report convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 (also known as mda-5 or Helicard) on chromosome 2q24.3. We found the association in an interim analysis of a genome-wide nonsynonymous SNP (nsSNP) scan, and we validated it in a case-control collection and replicated it in an independent family collection. In 4,253 cases, 5,842 controls and 2,134 parent-child trio genotypes, the risk ratio for the minor allele of the nsSNP rs1990760 A --> G (A946T) was 0.86 (95% confidence interval = 0.82-0.90) at P = 1.42 x 10(-10). 相似文献
62.
Todd JA Walker NM Cooper JD Smyth DJ Downes K Plagnol V Bailey R Nejentsev S Field SF Payne F Lowe CE Szeszko JS Hafler JP Zeitels L Yang JH Vella A Nutland S Stevens HE Schuilenburg H Coleman G Maisuria M Meadows W Smink LJ Healy B Burren OS Lam AA Ovington NR Allen J Adlem E Leung HT Wallace C Howson JM Guja C Ionescu-Tîrgovişte C;Genetics of Type Diabetes in Finland Simmonds MJ Heward JM Gough SC;Wellcome Trust Case Control Consortium Dunger DB Wicker LS Clayton DG 《Nature genetics》2007,39(7):857-864
The Wellcome Trust Case Control Consortium (WTCCC) primary genome-wide association (GWA) scan on seven diseases, including the multifactorial autoimmune disease type 1 diabetes (T1D), shows associations at P < 5 x 10(-7) between T1D and six chromosome regions: 12q24, 12q13, 16p13, 18p11, 12p13 and 4q27. Here, we attempted to validate these and six other top findings in 4,000 individuals with T1D, 5,000 controls and 2,997 family trios independent of the WTCCC study. We confirmed unequivocally the associations of 12q24, 12q13, 16p13 and 18p11 (P(follow-up) 相似文献
63.
Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 are associated with systemic lupus erythematosus 总被引:1,自引:0,他引:1
Lee-Kirsch MA Gong M Chowdhury D Senenko L Engel K Lee YA de Silva U Bailey SL Witte T Vyse TJ Kere J Pfeiffer C Harvey S Wong A Koskenmies S Hummel O Rohde K Schmidt RE Dominiczak AF Gahr M Hollis T Perrino FW Lieberman J Hübner N 《Nature genetics》2007,39(9):1065-1067
TREX1 acts in concert with the SET complex in granzyme A-mediated apoptosis, and mutations in TREX1 cause Aicardi-Goutières syndrome and familial chilblain lupus. Here, we report monoallelic frameshift or missense mutations and one 3' UTR variant of TREX1 present in 9/417 individuals with systemic lupus erythematosus but absent in 1,712 controls (P = 4.1 x 10(-7)). We demonstrate that two mutant TREX1 alleles alter subcellular targeting. Our findings implicate TREX1 in the pathogenesis of SLE. 相似文献
64.
Schulz O Diebold SS Chen M Näslund TI Nolte MA Alexopoulou L Azuma YT Flavell RA Liljeström P Reis e Sousa C 《Nature》2005,433(7028):887-892
Cross-presentation of cell-associated antigens plays an important role in regulating CD8+ T cell responses to proteins that are not expressed by antigen-presenting cells (APCs). Dendritic cells are the principal cross-presenting APCs in vivo and much progress has been made in elucidating the pathways that allow dendritic cells to capture and process cellular material. However, little is known about the signals that determine whether such presentation ultimately results in a cytotoxic T cell (CTL) response (cross-priming) or in CD8+ T cell inactivation (cross-tolerance). Here we describe a mechanism that promotes cross-priming during viral infections. We show that murine CD8alpha+ dendritic cells are activated by double-stranded (ds)RNA present in virally infected cells but absent from uninfected cells. Dendritic cell activation requires phagocytosis of infected material, followed by signalling through the dsRNA receptor, toll-like receptor 3 (TLR3). Immunization with virus-infected cells or cells containing synthetic dsRNA leads to a striking increase in CTL cross-priming against cell-associated antigens, which is largely dependent on TLR3 expression by antigen-presenting cells. Thus, TLR3 may have evolved to permit cross-priming of CTLs against viruses that do not directly infect dendritic cells. 相似文献
65.
Lymphatic vascular defects promoted by Prox1 haploinsufficiency cause adult-onset obesity 总被引:1,自引:0,他引:1
Harvey NL Srinivasan RS Dillard ME Johnson NC Witte MH Boyd K Sleeman MW Oliver G 《Nature genetics》2005,37(10):1072-1081
Multiple organs cooperate to regulate appetite, metabolism, and glucose and fatty acid homeostasis. Here, we identified and characterized lymphatic vasculature dysfunction as a cause of adult-onset obesity. We found that functional inactivation of a single allele of the homeobox gene Prox1 led to adult-onset obesity due to abnormal lymph leakage from mispatterned and ruptured lymphatic vessels. Prox1 heterozygous mice are a new model for adult-onset obesity and lymphatic vascular disease. 相似文献
66.
The theory of sexual selection was developed to explain the evolution of highly exaggerated sexual ornaments. Now supported by vast empirical evidence, sexual selection is generally considered to favour individuals with the most extreme trait expression. Here we describe disruptive selection on a sexual ornament, plumage coloration, in yearling male lazuli buntings (Passerina amoena). In habitats with limited good-quality nesting cover, the dullest and the brightest yearlings were more successful in obtaining high-quality territories, pairing with females and siring offspring, than yearlings with intermediate plumage. This pattern reflects the way that territorial adult males vary levels of aggression to influence the structure of their social neighbourhood. Adult males showed less aggression towards dull yearlings than intermediate and bright ones, permitting the dull yearlings to settle on good territories nearby. Fitness comparisons based on paternity analyses showed that both the adults and dull yearlings benefited genetically from this arrangement, revealing a rare example of sexually selected male-male cooperation. 相似文献
67.
68.
Perillartine and some derivatives: clarification of structures 总被引:1,自引:0,他引:1
69.
70.
Control of cell surface topography 总被引:14,自引:0,他引:14