全文获取类型
收费全文 | 223篇 |
免费 | 15篇 |
出版年
2021年 | 3篇 |
2020年 | 5篇 |
2018年 | 4篇 |
2017年 | 3篇 |
2016年 | 3篇 |
2015年 | 10篇 |
2014年 | 4篇 |
2013年 | 8篇 |
2012年 | 15篇 |
2011年 | 10篇 |
2010年 | 13篇 |
2009年 | 6篇 |
2008年 | 11篇 |
2007年 | 8篇 |
2006年 | 10篇 |
2005年 | 5篇 |
2004年 | 11篇 |
2003年 | 10篇 |
2002年 | 12篇 |
2001年 | 4篇 |
2000年 | 2篇 |
1999年 | 6篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1994年 | 3篇 |
1992年 | 6篇 |
1991年 | 3篇 |
1990年 | 3篇 |
1989年 | 3篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1983年 | 3篇 |
1982年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 2篇 |
1971年 | 3篇 |
1970年 | 1篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1966年 | 1篇 |
1965年 | 1篇 |
1964年 | 1篇 |
排序方式: 共有238条查询结果,搜索用时 15 毫秒
111.
Bruncko M Tahir SK Song X Chen J Ding H Huth JR Jin S Judge RA Madar DJ Park CH Park CM Petros AM Tse C Rosenberg SH Elmore SW 《Bioorganic & medicinal chemistry letters》2010,20(24):7503-7506
We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors (9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation. 相似文献
112.
Addo-Danso Shalom D. Defrenne Camille E. McCormack M. Luke Ostonen Ivika Addo-Danso Abigail Foli Ernest G. Borden Kira A. Isaac Marney E. Prescott Cindy E. 《Plant Ecology》2020,221(1):1-13
Plant Ecology - Key functions of fine roots are often related to their morphological traits, yet little is known about the patterns and controls on fine-root morphological traits in the tropical... 相似文献
113.
114.
115.
We have engineered the chemotaxis system of Escherichia coli to respond to molecules that are not attractants for wild‐type cells. The system depends on an artificially introduced enzymatic activity that converts the target molecule into a ligand for an E. coli chemoreceptor, thereby enabling the cells to respond to the new attractant. Two systems were designed, and both showed robust chemotactic responses in semisolid and liquid media. The first incorporates an asparaginase enzyme and the native E. coli aspartate receptor to produce a response to asparagine; the second uses penicillin acylase and an engineered chemoreceptor for phenylacetic acid to produce a response to phenylacetyl glycine. In addition, by taking advantage of a ‘hitchhiker’ effect in which cells producing the ligand can induce chemotaxis of neighboring cells lacking enzymatic activity, we were able to design a more complex system that functions as a simple microbial consortium. The result effectively introduces a logical ‘AND’ into the system so that the population only swims towards the combined gradients of two attractants. 相似文献
116.
I Kogan-Sakin Y Tabach Y Buganim A Molchadsky H Solomon S Madar I Kamer P Stambolsky A Shelly N Goldfinger S Valsesia-Wittmann A Puisieux A Zundelevich E N Gal-Yam C Avivi I Barshack M Brait D Sidransky E Domany V Rotter 《Cell death and differentiation》2011,18(2):271-281
A mutation within one allele of the p53 tumor suppressor gene can inactivate the remaining wild-type allele in a dominant-negative manner and in some cases can exert an additional oncogenic activity, known as mutant p53 ‘gain of function'' (GOF). To study the role of p53 mutations in prostate cancer and to discriminate between the dominant-negative effect and the GOF activity of mutant p53, we measured, using microarrays, the expression profiles of three immortalized prostate epithelial cultures expressing wild-type, inactivated p53 or mutated p53. Analysis of these gene expression profiles showed that both inactivated p53 and p53R175H mutant expression resulted in the upregulation of cell cycle progression genes. A second group, which was upregulated exclusively by mutant p53R175H, was predominantly enriched in developmental genes. This group of genes included the Twist1, a regulator of metastasis and epithelial–mesenchymal transition (EMT). Twist1 levels were also elevated in metastatic prostate cancer-derived cell line DU145, in immortalized lung fibroblasts and in a subset of lung cancer samples, all in a mutant p53-dependent manner. p53R175H mutant bearing immortalized epithelial cells showed typical features of EMT, such as higher expression of mesenchymal markers, lower expression of epithelial markers and enhanced invasive properties in vitro. The mechanism by which p53R175H mutant induces Twist1 expression involves alleviation of the epigenetic repression. Our data suggest that Twist1 expression might be upregulated following p53 mutation in cancer cells. 相似文献
117.
The theoretical framework for the field of cancer research is based on two main principles. The first is that cancer advances in a stepwise manner, with each alteration driving cells further toward a malignant state. Second, to cure cancer we must target only cancer-specific properties. Here, we analyze the birth and propagation of the cancer research paradigm. We believe the current paradigm is immersed in crisis and that the field would benefit from integrating theories within and outside the normal modes of research to compile a new framework, with the hope of faster progress and significantly fewer cancer-related deaths. 相似文献
118.
119.
120.