全文获取类型
收费全文 | 619篇 |
免费 | 52篇 |
国内免费 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 9篇 |
2021年 | 16篇 |
2020年 | 6篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 7篇 |
2016年 | 15篇 |
2015年 | 45篇 |
2014年 | 43篇 |
2013年 | 62篇 |
2012年 | 60篇 |
2011年 | 38篇 |
2010年 | 25篇 |
2009年 | 36篇 |
2008年 | 39篇 |
2007年 | 28篇 |
2006年 | 27篇 |
2005年 | 24篇 |
2004年 | 22篇 |
2003年 | 15篇 |
2002年 | 20篇 |
2001年 | 17篇 |
2000年 | 11篇 |
1999年 | 15篇 |
1998年 | 14篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1992年 | 5篇 |
1991年 | 4篇 |
1990年 | 4篇 |
1989年 | 3篇 |
1988年 | 2篇 |
1987年 | 2篇 |
1986年 | 2篇 |
1985年 | 5篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1976年 | 2篇 |
1971年 | 1篇 |
1967年 | 1篇 |
排序方式: 共有672条查询结果,搜索用时 31 毫秒
671.
Robert M. W. Hofstra Rein P. Stulp Tineke Stelwagen Charles H. C. M. Buys Ngan Ching Cheng Huib Caron Andries Westerveld Rogier Versteeg Claus Hansen Niels Tommerup Niels Clausen 《Human genetics》1996,97(3):362-364
Neuroblastoma occasionally occurs in diseases associated with abnormal neurocrest differentiation, e.g. Hirschsprung disease. Expression studies in developing mice suggest that the proto-oncogeneRET plays a role in neurocrest differentiation. In humans expression ofRET is limited to certain tumor types, including neuroblastoma, that derive from migrating neural crest cells. Mutations ofRET are found associated with Hirschsprung disease. These data prompted us to investigate expression ofRET and to search for gene mutations in neuroblastoma. Out of 16 neuroblastoma cell lines analyzed, 9 show clear expression ofRET in a Northern blot analysis. In a single-strand conformation polymorphism (SSCP) analysis of all exons, no mutations were detected other than neutral polymorphisms. In a patient with neuroblastoma, from a family in which different neurocrestopathies, including neuroblastoma and Hirschsprung disease, had occurred, we also failed to detect RET mutations. Possibly, expression ofRET in neuroblastoma merely reflects the differentiation status of the tumor cells. The absence of mutations suggests thatRET does not play a crucial role in the tumorigenesis of neuroblastoma. 相似文献
672.
Directed evolution of a glutaryl acylase into an adipyl acylase. 总被引:2,自引:0,他引:2
Charles F Sio Anja M Riemens Jan-Metske van der Laan Raymond M D Verhaert Wim J Quax 《European journal of biochemistry》2002,269(18):4495-4504
Semi-synthetic cephalosporin antibiotics belong to the top 10 of most sold drugs, and are produced from 7-aminodesacetoxycephalosporanic acid (7-ADCA). Recently new routes have been developed which allow for the production of adipyl-7-ADCA by a novel fermentation process. To complete the biosynthesis of 7-ADCA a highly active adipyl acylase is needed for deacylation of the adipyl derivative. Such an adipyl acylase can be generated from known glutaryl acylases. The glutaryl acylase of Pseudomonas SY-77 was mutated in a first round by exploration mutagenesis. For selection the mutants were grown on an adipyl substrate. The residues that are important to the adipyl acylase activity were identified, and in a second round saturation mutagenesis of this selected stretch of residues yielded variants with a threefold increased catalytic efficiency. The effect of the mutations could be rationalized on hindsight by the 3D structure of the acylase. In conclusion, the substrate specificity of a dicarboxylic acid acylase was shifted towards adipyl-7-ADCA by a two-step directed evolution strategy. Although derivatives of the substrate were used for selection, mutants retained activity on the beta-lactam substrate. The strategy herein described may be generally applicable to all beta-lactam acylases. 相似文献