首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   611篇
  免费   6篇
  国内免费   5篇
系统科学   6篇
教育与普及   3篇
理论与方法论   8篇
现状及发展   64篇
研究方法   101篇
综合类   410篇
自然研究   30篇
  2022年   1篇
  2021年   2篇
  2020年   2篇
  2019年   3篇
  2018年   1篇
  2017年   5篇
  2016年   8篇
  2015年   3篇
  2014年   5篇
  2013年   17篇
  2012年   85篇
  2011年   110篇
  2010年   17篇
  2009年   7篇
  2008年   73篇
  2007年   55篇
  2006年   36篇
  2005年   44篇
  2004年   34篇
  2003年   49篇
  2002年   45篇
  1999年   6篇
  1998年   4篇
  1996年   2篇
  1993年   1篇
  1992年   1篇
  1988年   1篇
  1987年   2篇
  1985年   1篇
  1982年   1篇
  1981年   1篇
排序方式: 共有622条查询结果,搜索用时 218 毫秒
91.
92.
E Hand 《Nature》2012,487(7408):420
  相似文献   
93.
Hand E 《Nature》2012,481(7380):127
  相似文献   
94.
E Hand 《Nature》2012,488(7412):442-443
  相似文献   
95.
The Amazon basin in transition   总被引:7,自引:0,他引:7  
Agricultural expansion and climate variability have become important agents of disturbance in the Amazon basin. Recent studies have demonstrated considerable resilience of Amazonian forests to moderate annual drought, but they also show that interactions between deforestation, fire and drought potentially lead to losses of carbon storage and changes in regional precipitation patterns and river discharge. Although the basin-wide impacts of land use and drought may not yet surpass the magnitude of natural variability of hydrologic and biogeochemical cycles, there are some signs of a transition to a disturbance-dominated regime. These signs include changing energy and water cycles in the southern and eastern portions of the Amazon basin.  相似文献   
96.
Medulloblastoma, the most common malignant paediatric brain tumour, arises in the cerebellum and disseminates through the cerebrospinal fluid in the leptomeningeal space to coat the brain and spinal cord. Dissemination, a marker of poor prognosis, is found in up to 40% of children at diagnosis and in most children at the time of recurrence. Affected children therefore are treated with radiation to the entire developing brain and spinal cord, followed by high-dose chemotherapy, with the ensuing deleterious effects on the developing nervous system. The mechanisms of dissemination through the cerebrospinal fluid are poorly studied, and medulloblastoma metastases have been assumed to be biologically similar to the primary tumour. Here we show that in both mouse and human medulloblastoma, the metastases from an individual are extremely similar to each other but are divergent from the matched primary tumour. Clonal genetic events in the metastases can be demonstrated in a restricted subclone of the primary tumour, suggesting that only rare cells within the primary tumour have the ability to metastasize. Failure to account for the bicompartmental nature of metastatic medulloblastoma could be a major barrier to the development of effective targeted therapies.  相似文献   
97.
Hand E 《Nature》2012,485(7398):290-291
  相似文献   
98.
Chromatin-modifying enzymes as modulators of reprogramming   总被引:2,自引:0,他引:2  
  相似文献   
99.
100.
Effective targeted cancer therapeutic development depends upon distinguishing disease-associated 'driver' mutations, which have causative roles in malignancy pathogenesis, from 'passenger' mutations, which are dispensable for cancer initiation and maintenance. Translational studies of clinically active targeted therapeutics can definitively discriminate driver from passenger lesions and provide valuable insights into human cancer biology. Activating internal tandem duplication (ITD) mutations in FLT3 (FLT3-ITD) are detected in approximately 20% of acute myeloid leukaemia (AML) patients and are associated with a poor prognosis. Abundant scientific and clinical evidence, including the lack of convincing clinical activity of early FLT3 inhibitors, suggests that FLT3-ITD probably represents a passenger lesion. Here we report point mutations at three residues within the kinase domain of FLT3-ITD that confer substantial in vitro resistance to AC220 (quizartinib), an active investigational inhibitor of FLT3, KIT, PDGFRA, PDGFRB and RET; evolution of AC220-resistant substitutions at two of these amino acid positions was observed in eight of eight FLT3-ITD-positive AML patients with acquired resistance to AC220. Our findings demonstrate that FLT3-ITD can represent a driver lesion and valid therapeutic target in human AML. AC220-resistant FLT3 kinase domain mutants represent high-value targets for future FLT3 inhibitor development efforts.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号