全文获取类型
收费全文 | 345篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 5篇 |
理论与方法论 | 2篇 |
现状及发展 | 49篇 |
研究方法 | 37篇 |
综合类 | 241篇 |
自然研究 | 12篇 |
出版年
2019年 | 2篇 |
2017年 | 1篇 |
2016年 | 2篇 |
2015年 | 2篇 |
2013年 | 1篇 |
2012年 | 16篇 |
2011年 | 24篇 |
2010年 | 4篇 |
2009年 | 2篇 |
2008年 | 11篇 |
2007年 | 20篇 |
2006年 | 13篇 |
2005年 | 14篇 |
2004年 | 10篇 |
2003年 | 4篇 |
2002年 | 8篇 |
2001年 | 7篇 |
2000年 | 13篇 |
1999年 | 2篇 |
1997年 | 1篇 |
1996年 | 1篇 |
1994年 | 1篇 |
1992年 | 11篇 |
1991年 | 5篇 |
1990年 | 12篇 |
1989年 | 8篇 |
1988年 | 4篇 |
1987年 | 8篇 |
1986年 | 12篇 |
1985年 | 9篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 7篇 |
1978年 | 3篇 |
1977年 | 9篇 |
1976年 | 3篇 |
1975年 | 6篇 |
1974年 | 10篇 |
1973年 | 5篇 |
1972年 | 7篇 |
1971年 | 11篇 |
1970年 | 7篇 |
1969年 | 3篇 |
1968年 | 9篇 |
1967年 | 8篇 |
1966年 | 4篇 |
1965年 | 6篇 |
排序方式: 共有346条查询结果,搜索用时 15 毫秒
341.
Russ AP Wattler S Colledge WH Aparicio SA Carlton MB Pearce JJ Barton SC Surani MA Ryan K Nehls MC Wilson V Evans MJ 《Nature》2000,404(6773):95-99
The earliest cell fate decision in the mammalian embryo separates the extra-embryonic trophoblast lineage, which forms the fetal portion of the placenta, from the embryonic cell lineages. The body plan of the embryo proper is established only later at gastrulation, when the pluripotent epiblast gives rise to the germ layers ectoderm, mesoderm and endoderm. Here we show that the T-box gene Eomesodermin performs essential functions in both trophoblast development and gastrulation. Mouse embryos lacking Eomesodermin arrest at the blastocyst stage. Mutant trophoectoderm does not differentiate into trophoblast, indicating that Eomesodermin may be required for the development of trophoblast stem cells. In the embryo proper, Eomesodermin is essential for mesoderm formation. Although the specification of the anterior-posterior axis and the initial response to mesoderm-inducing signals is intact in mutant epiblasts, the prospective mesodermal cells are not recruited into the primitive streak. Our results indicate that Eomesodermin defines a conserved molecular pathway controlling the morphogenetic movements of germ layer formation and has acquired a new function in mammals in the differentiation of trophoblast. 相似文献
342.
Humanized xenobiotic response in mice expressing nuclear receptor SXR 总被引:35,自引:0,他引:35
Xie W Barwick JL Downes M Blumberg B Simon CM Nelson MC Neuschwander-Tetri BA Brunt EM Guzelian PS Evans RM 《Nature》2000,406(6794):435-439
343.
Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells 总被引:1,自引:0,他引:1
Lister R Pelizzola M Kida YS Hawkins RD Nery JR Hon G Antosiewicz-Bourget J O'Malley R Castanon R Klugman S Downes M Yu R Stewart R Ren B Thomson JA Evans RM Ecker JR 《Nature》2011,471(7336):68-73
Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation. 相似文献
344.
ATP drives lamina propria T(H)17 cell differentiation 总被引:2,自引:0,他引:2
Atarashi K Nishimura J Shima T Umesaki Y Yamamoto M Onoue M Yagita H Ishii N Evans R Honda K Takeda K 《Nature》2008,455(7214):808-812
Interleukin (IL)-17-producing CD4(+) T lymphocytes (T(H)17 cells) constitute a subset of T-helper cells involved in host defence and several immune disorders. An intriguing feature of T(H)17 cells is their selective and constitutive presence in the intestinal lamina propria. Here we show that adenosine 5'-triphosphate (ATP) that can be derived from commensal bacteria activates a unique subset of lamina propria cells, CD70(high)CD11c(low) cells, leading to the differentiation of T(H)17 cells. Germ-free mice exhibit much lower concentrations of luminal ATP, accompanied by fewer lamina propria T(H)17 cells, compared to specific-pathogen-free mice. Systemic or rectal administration of ATP into these germ-free mice results in a marked increase in the number of lamina propria T(H)17 cells. A CD70(high)CD11c(low) subset of the lamina propria cells expresses T(H)17-prone molecules, such as IL-6, IL-23p19 and transforming-growth-factor-beta-activating integrin-alphaV and -beta8, in response to ATP stimulation, and preferentially induces T(H)17 differentiation of co-cultured naive CD4(+) T cells. The critical role of ATP is further underscored by the observation that administration of ATP exacerbates a T-cell-mediated colitis model with enhanced T(H)17 differentiation. These observations highlight the importance of commensal bacteria and ATP for T(H)17 differentiation in health and disease, and offer an explanation of why T(H)17 cells specifically present in the intestinal lamina propria. 相似文献
345.
Yang X Ongusaha PP Miles PD Havstad JC Zhang F So WV Kudlow JE Michell RH Olefsky JM Field SJ Evans RM 《Nature》2008,451(7181):964-969
346.