全文获取类型
收费全文 | 627篇 |
免费 | 34篇 |
国内免费 | 5篇 |
专业分类
666篇 |
出版年
2024年 | 1篇 |
2023年 | 23篇 |
2022年 | 43篇 |
2021年 | 50篇 |
2020年 | 16篇 |
2019年 | 22篇 |
2018年 | 18篇 |
2017年 | 7篇 |
2016年 | 23篇 |
2015年 | 31篇 |
2014年 | 37篇 |
2013年 | 35篇 |
2012年 | 55篇 |
2011年 | 41篇 |
2010年 | 25篇 |
2009年 | 20篇 |
2008年 | 19篇 |
2007年 | 23篇 |
2006年 | 26篇 |
2005年 | 13篇 |
2004年 | 22篇 |
2003年 | 20篇 |
2002年 | 13篇 |
2001年 | 10篇 |
2000年 | 7篇 |
1999年 | 16篇 |
1998年 | 3篇 |
1997年 | 2篇 |
1996年 | 1篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1989年 | 6篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 1篇 |
1984年 | 4篇 |
1983年 | 4篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1976年 | 1篇 |
1975年 | 1篇 |
排序方式: 共有666条查询结果,搜索用时 0 毫秒
641.
Marshall S Duong T Wu T Hering MA Yada J Higgins S Orbus RJ Yan ZH Rumberger JM 《Analytical biochemistry》2003,319(2):304-313
We have created a stable, tetracycline-inducible HeLa cell line that overexpresses murine uridine diphosphate-N-acetylglucosaminyl transferase (OGT). Tetracycline increased cytosolic OGT activity about 4-fold in a dose-dependent manner (ED(50)=0.03 microg/ml) with enhanced activity observable at 8h and maximal activity observable by 40h. Enhanced OGT activity was due to overexpression of OGT protein as determined by Western analysis. Trichostatin A (TSA), a potent and specific histone deacetylase inhibitor (HDI), markedly enhanced tetracycline-induced OGT gene expression, resulting in a >10-fold increase in OGT activity (>50-fold compared to that of uninduced cells). Other HDIs such as butyrate (ED(50)=1.6mM) and propionate (ED(50)=8mM) were similarly effective, but less potent than TSA (ED(50)=120 nM). We next examined the appearance of recombinant OGT in cytosol and nucleosol at various times (10 min to 6h) after inducing OGT gene. Within 2h, recombinant OGT was detected by Western analysis in both cytosol and nucleosol. This indicates rapid biosynthesis and accumulation of recombinant OGT in the cytosol and subsequent nuclear translocation. Entry of OGT into the nucleus was closely correlated with enhanced O-linked glycosylation of nuclear proteins, indicating that recombinant OGT was enzymatically active. The ability to rapidly induce OGT expression in a stable cell line provides an excellent model system to study the mechanism(s) underlying OGT nuclear translocation and a useful system to elucidate the cascade of signaling events related to O-linked glycosylation. 相似文献
642.
Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry 总被引:1,自引:0,他引:1
Peng J Kim MJ Cheng D Duong DM Gygi SP Sheng M 《The Journal of biological chemistry》2004,279(20):21003-21011
The postsynaptic density (PSD) of central excitatory synapses plays a key role in postsynaptic signal transduction and contains a high concentration of glutamate receptors and associated scaffold and signaling proteins. We report here a comprehensive analysis of purified PSD fractions by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We identified 374 different proteins that copurified with the PSD structure and discovered thirteen phosphorylated sites from eight proteins. These proteins were classified into numerous functional groups, implying that the signaling pathways in the PSD are complex and diverse. Furthermore, using quantitative mass spectrometry, we measured the molar concentration and relative stoichiometries of a number of glutamate receptor subunits and scaffold proteins in the postsynaptic density. Thus this proteomic study reveals crucial information about molecular abundance as well as molecular diversity in the PSD, and provides a basis for further studies on the molecular mechanisms of synaptic function and plasticity. 相似文献
643.
Wang J Breslin MJ Coleman PJ Duggan ME Hunt CA Hutchinson JH Leu CT Rodan SB Rodan GA Duong le T Hartman GD 《Bioorganic & medicinal chemistry letters》2004,14(4):1049-1052
A series of 3-substituted tetrahydro-[1,8]naphthyridine containing alpha(v)beta(3) antagonists was prepared. A comparison of their in vitro IC(50) values to the electron properties of the 3-substituents revealed a good linear Hammett correlation (rho=-1.96, R(2)=0.959). Electron-withdrawing groups at the 3-position of the tetrahydro-[1,8]naphthyridine decreased potency while electron-donating groups enhanced potency. 相似文献
644.
Breslin MJ Duggan ME Halczenko W Hartman GD Duong le T Fernandez-Metzler C Gentile MA Kimmel DB Leu CT Merkle K Prueksaritanont T Rodan GA Rodan SB Hutchinson JH 《Bioorganic & medicinal chemistry letters》2004,14(17):4515-4518
Subtle modifications were incorporated into the structure of clinical candidate 1. These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This approach led to the identification of 4 as a potent, selective alphaVbeta3 receptor antagonist that was selected for clinical development based on an improved PK profile and efficacy demonstrated in an in vivo model of bone turnover. 相似文献
645.
646.
647.
648.
Ngoc-Hong Nguyen Thuc-Huy Duong Huy Truong Nguyen Y Thien Vu Thi-Minh-Dinh Tran Thi-Thanh-Van Ho Chi-Cong Mai Dinh-Tri Mai Hoang-Chuong Nguyen Huong Thuy Le Duc-Dung Pham 《化学与生物多样性》2023,20(7):e202300390
Adenosma bracteosum and Vitex negundo are natural sources of methoxylated flavonoids. Little is known about the α-glucosidase inhibition of multi-methoxylated flavonoid derivatives. Eighteen natural flavonoids were isolated from A. bracteosum and V. negundo. Seven halogenated derivatives were synthesized. Their chemical structures were elucidated by extensive NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. All compounds were evaluated for their α-glucosidase inhibition. Most compounds showed good activity with IC50 values ranging from 16.7 to 421.8 μM. 6,8-Dibromocatechin was the most active compound with an IC50 value of 16.7 μM. A molecular docking study was conducted, indicating that those compounds are potent α-glucosidase inhibitors. 相似文献
649.
Xuan Tham Le Quoc Hung Nguyen Le Ngoc Duong Pham Van Hop Duong Bryn T. M. Dentinger Jean-Marc Moncalvo 《Mycological Progress》2012,11(3):775-780
The polypore genus Tomophagus was created to segregate one peculiar species, Ganoderma colossum, from the genus Ganoderma. Recent molecular studies have established the validity of this monotypic genus. Here we report the discovery of a second species of Tomophagus, T. cattienensis sp. nov., from Cat Tien National Park in southern Vietnam, a lowland forest that has been designated as a Biosphere Reserve by the United Nations Educational, Scientific and Cultural Organization (UNESCO). Recognition of this new species is based on combined evidence from morphology, cultural characteristics, and ITS rDNA barcodes. The discovery of this new species may have implications for the discovery of novel bioactive compounds for pharmaceutical use and/or for the pulp industry. 相似文献
650.
P Xu H Tan DM Duong Y Yang J Kupsco KH Moberg H Li P Jin J Peng 《Journal of proteome research》2012,11(9):4403-4412
Drosophila melanogaster is a common animal model for genetics studies, and quantitative proteomics studies of the fly are emerging. Here, we present in detail the development of a procedure to incorporate stable isotope-labeled amino acids into the fly proteome. In the method of stable isotope labeling with amino acids in Drosophila melanogaster (SILAC fly), flies were fed with SILAC-labeled yeast grown with modified media, enabling near complete labeling in a single generation. Biological variation in the proteome among individual flies was evaluated in a series of null experiments. We further applied the SILAC fly method to profile proteins from a model of fragile X syndrome, the most common cause of inherited mental retardation in human. The analysis identified a number of altered proteins in the disease model, including actin-binding protein profilin and microtubulin-associated protein futsch. The change of both proteins was validated by immunoblotting analysis. Moreover, we extended the SILAC fly strategy to study the dynamics of protein ubiquitination during the fly life span (from day 1 to day 30), by measuring the level of ubiquitin along with two major polyubiquitin chains (K48 and K63 linkages). The results show that the abundance of protein ubiquitination and the two major linkages do not change significantly within the measured age range. Together, the data demonstrate the application of the SILAC principle in D. melanogaster, facilitating the integration of powerful fly genomics with emerging proteomics. 相似文献