全文获取类型
收费全文 | 108篇 |
免费 | 9篇 |
国内免费 | 1篇 |
专业分类
118篇 |
出版年
2022年 | 1篇 |
2021年 | 2篇 |
2018年 | 2篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 2篇 |
2014年 | 7篇 |
2013年 | 8篇 |
2012年 | 11篇 |
2011年 | 4篇 |
2010年 | 10篇 |
2009年 | 6篇 |
2008年 | 7篇 |
2007年 | 3篇 |
2006年 | 7篇 |
2005年 | 3篇 |
2004年 | 2篇 |
2003年 | 5篇 |
2002年 | 3篇 |
2001年 | 4篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 4篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 3篇 |
1990年 | 1篇 |
1988年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1979年 | 2篇 |
1977年 | 1篇 |
排序方式: 共有118条查询结果,搜索用时 15 毫秒
91.
Donzelli M Busino L Chiesa M Ganoth D Hershko A Draetta GF 《Cell cycle (Georgetown, Tex.)》2004,3(4):469-471
We have recently demonstrated that regulation of Cdc25A protein abundance during S phase and in response to DNA damage is mediated by SCF(betaTrCP) activity. Based on sequence homology of known betaTrCP substrates, we found that Cdc25A contains a conserved motif (DSG), phosphorylation of which is required for interaction with betaTrCP.1 Here, we show that phosphorylation at Ser 82 within the DSG motif anchors Cdc25A to betaTrCP and that Chk1-dependent phosphorylation at Ser 76 affects this interaction as well as betaTrCP-dependent degradation. We propose that a hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. According to our model, phosphorylation at Ser 76 is a "priming" step required for Ser 82 phosphorylation, which in turn allows recruitment of Cdc25A by betaTrCP and subsequent betaTrCP-dependent degradation. 相似文献
92.
93.
94.
95.
Donzelli S Espey MG Flores-Santana W Switzer CH Yeh GC Huang J Stuehr DJ King SB Miranda KM Wink DA 《Free radical biology & medicine》2008,45(5):578-584
The chemical reactivity, toxicology, and pharmacological responses to nitroxyl (HNO) are often distinctly different from those of nitric oxide (NO). The discovery that HNO donors may have pharmacological utility for treatment of cardiovascular disorders such as heart failure and ischemia reperfusion has led to increased speculation of potential endogenous pathways for HNO biosynthesis. Here, the ability of heme proteins to utilize H(2)O(2) to oxidize hydroxylamine (NH(2)OH) or N-hydroxy-L-arginine (NOHA) to HNO was examined. Formation of HNO was evaluated with a recently developed selective assay in which the reaction products in the presence of reduced glutathione (GSH) were quantified by HPLC. Release of HNO from the heme pocket was indicated by formation of sulfinamide (GS(O)NH(2)), while the yields of nitrite and nitrate signified the degree of intramolecular recombination of HNO with the heme. Formation of GS(O)NH(2) was observed upon oxidation of NH(2)OH, whereas NOHA, the primary intermediate in oxidation of L-arginine by NO synthase, was apparently resistant to oxidation by the heme proteins utilized. In the presence of NH(2)OH, the highest yields of GS(O)NH(2) were observed with proteins in which the heme was coordinated to a histidine (horseradish peroxidase, lactoperoxidase, myeloperoxidase, myoglobin, and hemoglobin) in contrast to a tyrosine (catalase) or cysteine (cytochrome P450). That peroxidation of NH(2)OH by horseradish peroxidase produced free HNO, which was able to affect intracellular targets, was verified by conversion of 4,5-diaminofluorescein to the corresponding fluorophore within intact cells. 相似文献
96.
Mitogenic activity of pituitary hormones on cell cultures of normal and carcinogen-induced tumor epithelium from rat mammary glands 总被引:3,自引:2,他引:3 下载免费PDF全文
Cell suspension containing normal or tumor epithelium were readily obtained by enzymatically digesting rat mammary glands from perphenazine-treated (prolactin-hypersecreting) cycling, female virgin animals or hormone- responsive mammary tumors from animal treated with dimethylbenzanthracene. Cell suspensions were fractioned into predominantly epithelial and predominantly stromal cells by their differential rates of attachment to culture dishes. Both normal mammary and tumor epithelial cells were characterized by the presence of specific cell-junctional complexes, desmosome-like structures, surface microvilli, and their ability to synthesize casein. Serum-dependent protease activity was greater in cultures derived from tumors, and cells from such cultures grew in agarose whereas those from the non-neoplastic gland did not. The addition of prolactin to the culture medium stimulated DNA synthesis in primary or secondary epithelial cultures from tumors, whereas additional insulin and hydrocortisone with prolactin were required for similar levels of DNA synthesis in cultures from non-neoplastic glands. The fraction of cells synthesizing DNA was, however, smaller than that with 10 percent serum measured in the same time period. Both growth hormone and epidermal growth factor stimulated DNA synthesis but to a lesser extent than did prolactin. Prolactin with hydrocortisone and insulin were relatively inactive in promoting DNA synthesis of the nonepithelial cells whereas pituitary fibroblast growth factor was more active. These mitogenic effects were obtained when the hormones were added to the medium at near physiological concentrations, and paralleled the known activities of the hormones in control of mammary gland growth and development in the rat. 相似文献
97.
Background
The nucleus, a highly organized organelle, plays important role in cellular homeostasis. The nuclear proteins are crucial for chromosomal maintenance/segregation, gene expression, RNA processing/export, and many other processes. Several methods have been developed for predicting the nuclear proteins in the past. The aim of the present study is to develop a new method for predicting nuclear proteins with higher accuracy. 相似文献98.
Sara Donzelli Francesca Biagioni Francesca Fausti Sabrina Strano Giulia Fontemaggi Giovanni Blandino 《Current Genomics》2008,9(3):200-207
Cancer is caused by the spatial and temporal accumulation of alterations in the genome of a given cell. This leads to the deregulation of key signalling pathways that play a pivotal role in the control of cell proliferation and cell fate. The p53 tumor suppressor gene is the most frequent target in genetic alterations in human cancers. The primary selective advantage of such mutations is the elimination of cellular wild type p53 activity. In addition, many evidences in vitro and in vivo have demonstrated that at least certain mutant forms of p53 may possess a gain of function, whereby they contribute positively to cancer progression. The fine mapping and deciphering of specific cancer phenotypes is taking advantage of molecular-profiling studies based on genome-wide approaches. Currently, high-throughput methods such as array-based comparative genomic hybridization (CGH array), single nucleotide polymorphism array (SNP array), expression arrays and ChIP-on-chip arrays are available to study mutant p53-associated alterations in human cancers. Here we will mainly focus on the integration of the results raised through oncogenomic platforms that aim to shed light on the molecular mechanisms underlying mutant p53 gain of function activities and to provide useful information on the molecular stratification of tumor patients. 相似文献
99.
Hemicellulases and auxiliary enzymes for improved conversion of lignocellulosic biomass to monosaccharides 总被引:1,自引:0,他引:1
Dahai Gao Nirmal Uppugundla Shishir PS Chundawat Xiurong Yu Spencer Hermanson Krishne Gowda Phillip Brumm David Mead Venkatesh Balan Bruce E Dale 《Biotechnology for biofuels》2011,4(1):5
Background
High enzyme loading is a major economic bottleneck for the commercial processing of pretreated lignocellulosic biomass to produce fermentable sugars. Optimizing the enzyme cocktail for specific types of pretreated biomass allows for a significant reduction in enzyme loading without sacrificing hydrolysis yield. This is especially important for alkaline pretreatments such as Ammonia fiber expansion (AFEX) pretreated corn stover. Hence, a diverse set of hemicellulases supplemented along with cellulases is necessary for high recovery of monosaccharides. 相似文献100.
Oguz Bolgi Maria SilvaGarcia Breyan Ross Esther Pilla Vijayalakshmi Kari Markus Killisch Melanie Spitzner Nadine Stark Christof Lenz Konstantin Weiss Laura Donzelli Mark D Gorrell Marian Grade Jan Riemer Henning Urlaub Matthias Dobbelstein Robert Huber Ruth GeissFriedlander 《EMBO reports》2022,23(10)
N‐terminal sequences are important sites for post‐translational modifications that alter protein localization, activity, and stability. Dipeptidyl peptidase 9 (DPP9) is a serine aminopeptidase with the rare ability to cleave off N‐terminal dipeptides with imino acid proline in the second position. Here, we identify the tumor‐suppressor BRCA2 as a DPP9 substrate and show this interaction to be induced by DNA damage. We present crystallographic structures documenting intracrystalline enzymatic activity of DPP9, with the N‐terminal Met1‐Pro2 of a BRCA21‐40 peptide captured in its active site. Intriguingly, DPP9‐depleted cells are hypersensitive to genotoxic agents and are impaired in the repair of DNA double‐strand breaks by homologous recombination. Mechanistically, DPP9 targets BRCA2 for degradation and promotes the formation of RAD51 foci, the downstream function of BRCA2. N‐terminal truncation mutants of BRCA2 that mimic a DPP9 product phenocopy reduced BRCA2 stability and rescue RAD51 foci formation in DPP9‐deficient cells. Taken together, we present DPP9 as a regulator of BRCA2 stability and propose that by fine‐tuning the cellular concentrations of BRCA2, DPP9 alters the BRCA2 interactome, providing a possible explanation for DPP9''s role in cancer. 相似文献