全文获取类型
收费全文 | 286篇 |
免费 | 0篇 |
专业分类
系统科学 | 57篇 |
教育与普及 | 1篇 |
理论与方法论 | 1篇 |
现状及发展 | 41篇 |
研究方法 | 16篇 |
综合类 | 156篇 |
自然研究 | 14篇 |
出版年
2021年 | 1篇 |
2018年 | 2篇 |
2017年 | 1篇 |
2016年 | 1篇 |
2015年 | 1篇 |
2013年 | 4篇 |
2012年 | 9篇 |
2011年 | 32篇 |
2010年 | 5篇 |
2009年 | 3篇 |
2008年 | 4篇 |
2007年 | 11篇 |
2006年 | 10篇 |
2005年 | 17篇 |
2004年 | 11篇 |
2003年 | 14篇 |
2002年 | 9篇 |
2001年 | 6篇 |
2000年 | 7篇 |
1999年 | 3篇 |
1998年 | 2篇 |
1997年 | 2篇 |
1996年 | 3篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 9篇 |
1992年 | 6篇 |
1991年 | 11篇 |
1990年 | 8篇 |
1989年 | 4篇 |
1988年 | 9篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 1篇 |
1983年 | 2篇 |
1979年 | 3篇 |
1978年 | 7篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1971年 | 5篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1968年 | 7篇 |
1967年 | 7篇 |
1966年 | 9篇 |
1965年 | 5篇 |
排序方式: 共有286条查询结果,搜索用时 15 毫秒
281.
Mutations truncating the EP300 acetylase in human cancers 总被引:21,自引:0,他引:21
282.
STING is a direct innate immune sensor of cyclic di-GMP 总被引:1,自引:0,他引:1
Burdette DL Monroe KM Sotelo-Troha K Iwig JS Eckert B Hyodo M Hayakawa Y Vance RE 《Nature》2011,478(7370):515-518
283.
Innate immune recognition of bacterial ligands by NAIPs determines inflammasome specificity 总被引:1,自引:0,他引:1
Inflammasomes are a family of cytosolic multiprotein complexes that initiate innate immune responses to pathogenic microbes by activating the caspase 1 protease. Although genetic data support a critical role for inflammasomes in immune defence and inflammatory diseases, the molecular basis by which individual inflammasomes respond to specific stimuli remains poorly understood. The inflammasome that contains the NLRC4 (NLR family, CARD domain containing 4) protein was previously shown to be activated in response to two distinct bacterial proteins, flagellin and PrgJ, a conserved component of pathogen-associated type III secretion systems. However, direct binding between NLRC4 and flagellin or PrgJ has never been demonstrated. A homologue of NLRC4, NAIP5 (NLR family, apoptosis inhibitory protein 5), has been implicated in activation of NLRC4 (refs 7-11), but is widely assumed to have only an auxiliary role, as NAIP5 is often dispensable for NLRC4 activation. However, Naip5 is a member of a small multigene family, raising the possibility of redundancy and functional specialization among Naip genes. Here we show in mice that different NAIP paralogues determine the specificity of the NLRC4 inflammasome for distinct bacterial ligands. In particular, we found that activation of endogenous NLRC4 by bacterial PrgJ requires NAIP2, a previously uncharacterized member of the NAIP gene family, whereas NAIP5 and NAIP6 activate NLRC4 specifically in response to bacterial flagellin. We dissected the biochemical mechanism underlying the requirement for NAIP proteins by use of a reconstituted NLRC4 inflammasome system. We found that NAIP proteins control ligand-dependent oligomerization of NLRC4 and that the NAIP2-NLRC4 complex physically associates with PrgJ but not flagellin, whereas NAIP5-NLRC4 associates with flagellin but not PrgJ. Our results identify NAIPs as immune sensor proteins and provide biochemical evidence for a simple receptor-ligand model for activation of the NAIP-NLRC4 inflammasomes. 相似文献
284.
Ocean circulation in a warming climate 总被引:4,自引:0,他引:4
285.
Zody MC Garber M Adams DJ Sharpe T Harrow J Lupski JR Nicholson C Searle SM Wilming L Young SK Abouelleil A Allen NR Bi W Bloom T Borowsky ML Bugalter BE Butler J Chang JL Chen CK Cook A Corum B Cuomo CA de Jong PJ DeCaprio D Dewar K FitzGerald M Gilbert J Gibson R Gnerre S Goldstein S Grafham DV Grocock R Hafez N Hagopian DS Hart E Norman CH Humphray S Jaffe DB Jones M Kamal M Khodiyar VK LaButti K Laird G Lehoczky J Liu X Lokyitsang T Loveland J Lui A Macdonald P Major JE Matthews L Mauceli E 《Nature》2006,440(7087):1045-1049
Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. 相似文献
286.