全文获取类型
收费全文 | 149篇 |
免费 | 0篇 |
国内免费 | 3篇 |
专业分类
系统科学 | 4篇 |
现状及发展 | 41篇 |
研究方法 | 33篇 |
综合类 | 51篇 |
自然研究 | 23篇 |
出版年
2018年 | 1篇 |
2016年 | 1篇 |
2014年 | 4篇 |
2013年 | 1篇 |
2012年 | 6篇 |
2011年 | 37篇 |
2010年 | 8篇 |
2008年 | 12篇 |
2007年 | 8篇 |
2006年 | 12篇 |
2005年 | 7篇 |
2004年 | 7篇 |
2003年 | 4篇 |
2002年 | 6篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1991年 | 1篇 |
1987年 | 1篇 |
1982年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 2篇 |
1976年 | 4篇 |
1975年 | 5篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 3篇 |
1970年 | 5篇 |
1968年 | 1篇 |
1967年 | 2篇 |
1966年 | 1篇 |
1964年 | 1篇 |
1962年 | 1篇 |
1961年 | 1篇 |
1960年 | 1篇 |
排序方式: 共有152条查询结果,搜索用时 62 毫秒
151.
Solit DB Garraway LA Pratilas CA Sawai A Getz G Basso A Ye Q Lobo JM She Y Osman I Golub TR Sebolt-Leopold J Sellers WR Rosen N 《Nature》2006,439(7074):358-362
The kinase pathway comprising RAS, RAF, mitogen-activated protein kinase kinase (MEK) and extracellular signal regulated kinase (ERK) is activated in most human tumours, often through gain-of-function mutations of RAS and RAF family members. Using small-molecule inhibitors of MEK and an integrated genetic and pharmacologic analysis, we find that mutation of BRAF is associated with enhanced and selective sensitivity to MEK inhibition when compared to either 'wild-type' cells or cells harbouring a RAS mutation. This MEK dependency was observed in BRAF mutant cells regardless of tissue lineage, and correlated with both downregulation of cyclin D1 protein expression and the induction of G1 arrest. Pharmacological MEK inhibition completely abrogated tumour growth in BRAF mutant xenografts, whereas RAS mutant tumours were only partially inhibited. These data suggest an exquisite dependency on MEK activity in BRAF mutant tumours, and offer a rational therapeutic strategy for this genetically defined tumour subtype. 相似文献
152.
Scherer SE Muzny DM Buhay CJ Chen R Cree A Ding Y Dugan-Rocha S Gill R Gunaratne P Harris RA Hawes AC Hernandez J Hodgson AV Hume J Jackson A Khan ZM Kovar-Smith C Lewis LR Lozado RJ Metzker ML Milosavljevic A Miner GR Montgomery KT Morgan MB Nazareth LV Scott G Sodergren E Song XZ Steffen D Lovering RC Wheeler DA Worley KC Yuan Y Zhang Z Adams CQ Ansari-Lari MA Ayele M Brown MJ Chen G Chen Z Clerc-Blankenburg KP Davis C Delgado O Dinh HH Draper H Gonzalez-Garay ML Havlak P Jackson LR Jacob LS 《Nature》2006,440(7082):346-351
Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents. 相似文献