全文获取类型
收费全文 | 584篇 |
免费 | 58篇 |
出版年
2024年 | 1篇 |
2023年 | 15篇 |
2022年 | 17篇 |
2021年 | 21篇 |
2020年 | 10篇 |
2019年 | 12篇 |
2018年 | 18篇 |
2017年 | 19篇 |
2016年 | 17篇 |
2015年 | 26篇 |
2014年 | 32篇 |
2013年 | 38篇 |
2012年 | 42篇 |
2011年 | 45篇 |
2010年 | 26篇 |
2009年 | 26篇 |
2008年 | 32篇 |
2007年 | 23篇 |
2006年 | 35篇 |
2005年 | 23篇 |
2004年 | 15篇 |
2003年 | 14篇 |
2002年 | 19篇 |
2001年 | 14篇 |
2000年 | 22篇 |
1999年 | 10篇 |
1998年 | 6篇 |
1997年 | 6篇 |
1996年 | 10篇 |
1995年 | 3篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1969年 | 1篇 |
排序方式: 共有642条查询结果,搜索用时 437 毫秒
41.
Yohei Takeda Vuong N. Bui Kenta Iwasaki Takaaki Kobayashi Haruko Ogawa Kunitoshi Imai 《Biochemical and biophysical research communications》2014
Macrophages play important roles in the host innate immune response and are involved in the onset of diseases caused by inflammation. Toll-like receptor 4 (TLR4)-mediated inflammatory responses of macrophages may be associated with diseases such as diabetes and diseases of the cardiovascular system. Hydroxytyrosol (HT) exerts strong antioxidant and anti-inflammatory effects and may be applied in the treatment of inflammatory diseases. In the present study conducted in vitro, we investigated the effects of the TLR4-dependent anti-inflammatory effect of HT on peritoneal macrophage of BALB/c mice. We show here that the elevated levels of iNOS gene expression and nitric oxide production induced by lipopolysaccharide (LPS) (0.25 μg/ml) were suppressed by HT (12.5 μg/ml). LPS-dependent NF-κB gene expression and phosphorylation of NF-κB were not affected by HT under these conditions. In contrast, the expression of TNF-α was significantly increased in the presence of LPS and HT. These results suggest that HT suppressed nitric oxide production by decreasing iNOS gene expression through a mechanism independent of the NF-κB signaling pathway. These novel findings suggest that the modulation by HT of the expression of genes involved in inflammation may involve multiple mechanisms. 相似文献
42.
Min Zhong Wang Shen Kenneth J. Barr Jennifer P. Arbitrario Michelle R. Arkin Minna Bui Teresa Chen Brian C. Cunningham Marc J. Evanchik Emily J. Hanan Ute Hoch Karen Huen Jennifer Hyde Jeffery L. Kumer Teresa Lac Chris E. Lawrence Jose R. Martell Johan D. Oslob Kumar Paulvannan Saileta Prabhu W. Mike Flanagan 《Bioorganic & medicinal chemistry letters》2010,20(17):5269-5273
This letter describes the discovery of a novel series of tetrahydroisoquinoline (THIQ)-derived small molecules that potently inhibit both human T-cell migration and super-antigen induced T-cell activation through disruption of the binding of integrin LFA-1 to its receptor, ICAM-1. In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat. Either intravenous administration of 6q or oral administration of its ethyl ester (6t) produced a significant reduction of neutrophil migration in a thioglycollate-induced murine peritonitis model. 相似文献
43.
Jun Sun Shelley A Haveman Olivia Bui Tom R Fahland Derek R Lovley 《BMC systems biology》2010,4(1):174
Background
Pelobacter species are commonly found in a number of subsurface environments, and are unique members of the Geobacteraceae family. They are phylogenetically intertwined with both Geobacter and Desulfuromonas species. Pelobacter species likely play important roles in the fermentative degradation of unusual organic matters and syntrophic metabolism in the natural environments, and are of interest for applications in bioremediation and microbial fuel cells. 相似文献44.
45.
Moutaftsi M Bui HH Peters B Sidney J Salek-Ardakani S Oseroff C Pasquetto V Crotty S Croft M Lefkowitz EJ Grey H Sette A 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(11):6814-6820
Recent studies have defined vaccinia virus (VACV)-specific CD8(+) T cell epitopes in mice and humans. However, little is known about the epitope specificities of CD4(+) T cell responses. In this study, we identified 14 I-A(b)-restricted VACV-specific CD4(+) T cell epitopes by screening a large set of 2146 different 15-mer peptides in C57BL/6 mice. These epitopes account for approximately 20% of the total anti-VACV CD4(+) T cell response and are derived from 13 different viral proteins. Surprisingly, none of the CD4(+) T cell epitopes identified was derived from VACV virulence factors. Although early Ags were recognized, late Ags predominated as CD4(+) T cell targets. These results are in contrast to what was previously found in CD8(+) T cells responses, where early Ags, including virulence factors, were prominently recognized. Taken together, these results highlight fundamental differences in immunodominance of CD4(+) and CD8(+) T cell responses to a complex pathogen. 相似文献
46.
Binh Tran Quang Linh Duong Tuan Chung Le Thi Kim Phuong Pham Tran Nga Bui Thi Thuy Ngoc Nguyen Anh Thuyen Tran Quang Tung Do Dinh Nhung Bui Thi 《Biochemical genetics》2022,60(2):707-719
Biochemical Genetics - The study aimed to evaluate the contribution of the FTO A/T polymorphism (rs9939609) to the prediction of the future type 2 diabetes (T2D). A population-based prospective... 相似文献
47.
Gilbert Richarme Mouadh Mihoub Julien Dairou Linh Chi Bui Thibaut Leger Aazdine Lamouri 《The Journal of biological chemistry》2015,290(3):1885-1897
Glycation is an inevitable nonenzymatic covalent reaction between proteins and endogenous reducing sugars or dicarbonyls (methylglyoxal, glyoxal) that results in protein inactivation. DJ-1 was reported to be a multifunctional oxidative stress response protein with poorly defined function. Here, we show that human DJ-1 is a protein deglycase that repairs methylglyoxal- and glyoxal-glycated amino acids and proteins by acting on early glycation intermediates and releases repaired proteins and lactate or glycolate, respectively. DJ-1 deglycates cysteines, arginines, and lysines (the three major glycated amino acids) of serum albumin, glyceraldehyde-3-phosphate dehydrogenase, aldolase, and aspartate aminotransferase and thus reactivates these proteins. DJ-1 prevented protein glycation in an Escherichia coli mutant deficient in the DJ-1 homolog YajL and restored cell viability in glucose-containing media. These results suggest that DJ-1-associated Parkinsonism results from excessive protein glycation and establishes DJ-1 as a major anti-glycation and anti-aging protein. 相似文献
48.
49.
The ubiquitin proteasome–proteolytic pathway has emerged as one of the most significant pathways in modulating protein homeostasis
under both normal and disease states. The use of proteasome inhibitors (PI) has played a pivotal role in understanding protein
turn over. The main objective of this work was to develop a comprehensive, fast, and reliable, yet simple in vitro assay that would allow for the identification and characterization of a wide range of PIs. The assays consist of a 96-well
plate high throughput (HTP) method to assess proteasome activity in Hs578T breast cancer cell extracts, purified 20S proteasome,
using a fluorogenic substrate, Suc-leu-leu-val-tyr-7-AMC, specific to the chymotrypsin-like enzymatic activity of the proteasome.
We showed that the chymotrypsin-like activity of the proteasome was inhibited in the two in vitro systems, albeit to different degrees. The assay system also includes two cell-based assays consisting of a vector expressing
a fusion protein of green fluorescent protein (gfp) and Mouse Ornithine Decarboxylase (MODC) in Zs578T (parental Hs578T carrying
the vector that expresses the fusion protein). In the cell-based assay analyses (qualitatively by microscopy and quantitatively
by flow cytometry), treatment of Zs578T with PIs prevented the degradation of MODC, accumulated gfp, indicative of increased
proteasome inhibition. Because no single assay represents a definitive proof of proteasome inhibitory activity, combined,
these assays should serve as a comprehensive benchmark for the identification and partial characterization of novel inhibitors.
In summary, the four-step assay protocol can easily be adapted into a high throughput format to rapidly screen unknown inhibitors. 相似文献
50.