全文获取类型
收费全文 | 433篇 |
免费 | 0篇 |
国内免费 | 1篇 |
专业分类
系统科学 | 6篇 |
教育与普及 | 3篇 |
理论与方法论 | 4篇 |
现状及发展 | 91篇 |
研究方法 | 49篇 |
综合类 | 277篇 |
自然研究 | 4篇 |
出版年
2020年 | 2篇 |
2018年 | 4篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 6篇 |
2013年 | 6篇 |
2012年 | 28篇 |
2011年 | 41篇 |
2010年 | 12篇 |
2009年 | 6篇 |
2008年 | 32篇 |
2007年 | 25篇 |
2006年 | 33篇 |
2005年 | 28篇 |
2004年 | 29篇 |
2003年 | 28篇 |
2002年 | 24篇 |
2001年 | 8篇 |
2000年 | 7篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1992年 | 2篇 |
1991年 | 3篇 |
1990年 | 2篇 |
1988年 | 2篇 |
1987年 | 3篇 |
1986年 | 4篇 |
1984年 | 3篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 3篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1974年 | 7篇 |
1973年 | 7篇 |
1972年 | 3篇 |
1971年 | 7篇 |
1970年 | 7篇 |
1969年 | 3篇 |
1968年 | 8篇 |
1967年 | 4篇 |
1965年 | 2篇 |
1961年 | 1篇 |
1960年 | 1篇 |
1958年 | 1篇 |
1955年 | 1篇 |
1954年 | 1篇 |
排序方式: 共有434条查询结果,搜索用时 17 毫秒
1.
2.
Zhang Z Lee JC Lin L Olivas V Au V LaFramboise T Abdel-Rahman M Wang X Levine AD Rho JK Choi YJ Choi CM Kim SW Jang SJ Park YS Kim WS Lee DH Lee JS Miller VA Arcila M Ladanyi M Moonsamy P Sawyers C Boggon TJ Ma PC Costa C Taron M Rosell R Halmos B Bivona TG 《Nature genetics》2012,44(8):852-860
Human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR frequently respond to treatment with EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, but responses are not durable, as tumors acquire resistance. Secondary mutations in EGFR (such as T790M) or upregulation of the MET kinase are found in over 50% of resistant tumors. Here, we report increased activation of AXL and evidence for epithelial-to-mesenchymal transition (EMT) in multiple in vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to erlotinib in the absence of the EGFR p.Thr790Met alteration or MET activation. Genetic or pharmacological inhibition of AXL restored sensitivity to erlotinib in these tumor models. Increased expression of AXL and, in some cases, of its ligand GAS6 was found in EGFR-mutant lung cancers obtained from individuals with acquired resistance to TKIs. These data identify AXL as a promising therapeutic target whose inhibition could prevent or overcome acquired resistance to EGFR TKIs in individuals with EGFR-mutant lung cancer. 相似文献
3.
Christian Dölle Marc Niere Emilia Lohndal Mathias Ziegler 《Cellular and molecular life sciences : CMLS》2010,67(3):433-443
Poly-ADP-ribose polymerases (PARPs) use NAD+ as substrate to generate polymers of ADP-ribose. We targeted the catalytic domain of human PARP1 as molecular NAD+ detector into cellular organelles. Immunochemical detection of polymers demonstrated distinct subcellular NAD+ pools in mitochondria, peroxisomes and, surprisingly, in the endoplasmic reticulum and the Golgi complex. Polymers did not
accumulate within the mitochondrial intermembrane space or the cytosol. We demonstrate the suitability of this compartment-specific
NAD+ and poly-ADP-ribose turnover to establish intra-organellar protein localization. For overexpressed proteins, genetically
endowed with PARP activity, detection of polymers indicates segregation from the cytosol and consequently intra-organellar
residence. In mitochondria, polymer build-up reveals matrix localization of the PARP fusion protein. Compared to presently
used fusion tags for subcellular protein localization, these are substantial improvements in resolution. We thus established
a novel molecular tool applicable for studies of subcellular NAD metabolism and protein localization. 相似文献
4.
Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} The putative intergeneric hybridization between Stansbury Cliffrose ( Cowania ) and Apache Plume ( Fallugia ) is found to be undocumented. Chromosome counts support reported base numbers for Cowania and Fallugia to be n = 9 and n = 14 respectively. 相似文献
5.
S Peña-Llopis S Vega-Rubín-de-Celis A Liao N Leng A Pavía-Jiménez S Wang T Yamasaki L Zhrebker S Sivanand P Spence L Kinch T Hambuch S Jain Y Lotan V Margulis AI Sagalowsky PB Summerour W Kabbani SW Wong N Grishin M Laurent XJ Xie CD Haudenschild MT Ross DR Bentley P Kapur J Brugarolas 《Nature genetics》2012,44(9):1072
6.
7.
8.
Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. 总被引:87,自引:0,他引:87
R E Phillips S Rowland-Jones D F Nixon F M Gotch J P Edwards A O Ogunlesi J G Elvin J A Rothbard C R Bangham C R Rizza 《Nature》1991,354(6353):453-459
In a longitudinal study of HIV seropositive patients, there were fluctuations in the specificity of cytotoxic T cells for the virus. This was matched by variability in proviral gag DNA epitope sequences in the lymphocytes of these patients. Some of these viral variants are not recognized by autologous T cells. Accumulation of such mutations in T-cell antigenic targets would provide a mechanism for immune escape. 相似文献
9.
10.