全文获取类型
收费全文 | 390篇 |
免费 | 2篇 |
国内免费 | 2篇 |
专业分类
系统科学 | 5篇 |
教育与普及 | 2篇 |
理论与方法论 | 2篇 |
现状及发展 | 28篇 |
研究方法 | 91篇 |
综合类 | 213篇 |
自然研究 | 53篇 |
出版年
2021年 | 1篇 |
2020年 | 1篇 |
2018年 | 3篇 |
2017年 | 3篇 |
2016年 | 2篇 |
2015年 | 3篇 |
2014年 | 7篇 |
2013年 | 4篇 |
2012年 | 33篇 |
2011年 | 100篇 |
2010年 | 11篇 |
2009年 | 2篇 |
2008年 | 30篇 |
2007年 | 40篇 |
2006年 | 33篇 |
2005年 | 21篇 |
2004年 | 29篇 |
2003年 | 18篇 |
2002年 | 35篇 |
2001年 | 1篇 |
2000年 | 4篇 |
1999年 | 3篇 |
1998年 | 1篇 |
1996年 | 1篇 |
1994年 | 2篇 |
1990年 | 2篇 |
1985年 | 1篇 |
1972年 | 1篇 |
1968年 | 1篇 |
1965年 | 1篇 |
排序方式: 共有394条查询结果,搜索用时 15 毫秒
41.
42.
Telomere length in humans is partly controlled by a feedback mechanism in which telomere elongation by telomerase is limited by the accumulation of the TRF1 complex at chromosome ends. TRF1 itself can be inhibited by the poly(ADP-ribose) polymerase (PARP) activity of its interacting partner tankyrase 1, which abolishes its DNA binding activity in vitro and removes the TRF1 complex from telomeres in vivo. Here we report that the inhibition of TRF1 by tankyrase is in turn controlled by a second TRF1-interacting factor, TIN2 (ref. 6). Partial knockdown of TIN2 by small hairpin RNA in a telomerase-positive cell line resulted in telomere elongation, which is typical of reduced TRF1 function. Transient inhibition of TIN2 with small interfering RNA led to diminished telomeric TRF1 signals. This effect could be reversed with the PARP inhibitor 3-aminobenzamide and did not occur in cells overexpressing a PARP-dead mutant of tankyrase 1. TIN2 formed a ternary complex with TRF1 and tankyrase 1 and stabilized their interaction, an effect also observed with the PARP-dead mutant of tankyrase 1. In vitro, TIN2 protected TRF1 from poly(ADP-ribosyl)ation by tankyrase 1 without affecting tankyrase 1 automodification. These data identify TIN2 as a PARP modulator in the TRF1 complex and can explain how TIN2 contributes to the regulation of telomere length. 相似文献
43.
44.
45.
The harlequin mouse mutation downregulates apoptosis-inducing factor 总被引:35,自引:0,他引:35
Klein JA Longo-Guess CM Rossmann MP Seburn KL Hurd RE Frankel WN Bronson RT Ackerman SL 《Nature》2002,419(6905):367-374
Harlequin (Hq) mutant mice have progressive degeneration of terminally differentiated cerebellar and retinal neurons. We have identified the Hq mutation as a proviral insertion in the apoptosis-inducing factor (Aif) gene, causing about an 80% reduction in AIF expression. Mutant cerebellar granule cells are susceptible to exogenous and endogenous peroxide-mediated apoptosis, but can be rescued by AIF expression. Overexpression of AIF in wild-type granule cells further decreases peroxide-mediated cell death, suggesting that AIF serves as a free radical scavenger. In agreement, dying neurons in aged Hq mutant mice show oxidative stress. In addition, neurons damaged by oxidative stress in both the cerebellum and retina of Hq mutant mice re-enter the cell cycle before undergoing apoptosis. Our results provide a genetic model of oxidative stress-mediated neurodegeneration and demonstrate a direct connection between cell cycle re-entry and oxidative stress in the ageing central nervous system. 相似文献
46.
47.
48.
The current 'standard model' of cosmology posits an infinite flat universe forever expanding under the pressure of dark energy. First-year data from the Wilkinson Microwave Anisotropy Probe (WMAP) confirm this model to spectacular precision on all but the largest scales. Temperature correlations across the microwave sky match expectations on angular scales narrower than 60 degrees but, contrary to predictions, vanish on scales wider than 60 degrees. Several explanations have been proposed. One natural approach questions the underlying geometry of space--namely, its curvature and topology. In an infinite flat space, waves from the Big Bang would fill the universe on all length scales. The observed lack of temperature correlations on scales beyond 60 degrees means that the broadest waves are missing, perhaps because space itself is not big enough to support them. Here we present a simple geometrical model of a finite space--the Poincaré dodecahedral space--which accounts for WMAP's observations with no fine-tuning required. The predicted density is Omega(0) approximately 1.013 > 1, and the model also predicts temperature correlations in matching circles on the sky. 相似文献
49.
Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia 总被引:3,自引:0,他引:3
Pollock PM Cohen-Solal K Sood R Namkoong J Martino JJ Koganti A Zhu H Robbins C Makalowska I Shin SS Marin Y Roberts KG Yudt LM Chen A Cheng J Incao A Pinkett HW Graham CL Dunn K Crespo-Carbone SM Mackason KR Ryan KB Sinsimer D Goydos J Reuhl KR Eckhaus M Meltzer PS Pavan WJ Trent JM Chen S 《Nature genetics》2003,34(1):108-112
50.
Cancer cells frequently have disease-specific chromosome rearrangements. It is poorly understood why translocations between chromosomes recur at specific breakpoints in the genome. Here we provide evidence that higher-order spatial genome organization is a contributing factor in the formation of recurrent translocations. We show that MYC, BCL and immunoglobulin loci, which are recurrently translocated in various B-cell lymphomas, are preferentially positioned in close spatial proximity relative to each other in normal B cells. Loci in spatial proximity are non-randomly positioned towards the nuclear interior in normal B cells. This locus proximity is the consequence of higher-order genome structure rather than a property of individual genes. Our results suggest that the formation of specific translocations in human lymphomas, and perhaps other tissues, is determined in part by higher-order spatial organization of the genome. 相似文献