全文获取类型
收费全文 | 247篇 |
免费 | 27篇 |
国内免费 | 1篇 |
出版年
2021年 | 6篇 |
2018年 | 6篇 |
2017年 | 7篇 |
2016年 | 8篇 |
2015年 | 8篇 |
2014年 | 6篇 |
2013年 | 6篇 |
2012年 | 10篇 |
2011年 | 12篇 |
2010年 | 11篇 |
2009年 | 9篇 |
2008年 | 11篇 |
2007年 | 9篇 |
2006年 | 9篇 |
2005年 | 5篇 |
2004年 | 7篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 7篇 |
1999年 | 3篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 7篇 |
1990年 | 4篇 |
1989年 | 6篇 |
1988年 | 5篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1985年 | 2篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 3篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1972年 | 4篇 |
1970年 | 4篇 |
1969年 | 5篇 |
1968年 | 2篇 |
1965年 | 2篇 |
1920年 | 2篇 |
排序方式: 共有275条查询结果,搜索用时 15 毫秒
161.
162.
I Prieto-Potín JA Roman-Blas MJ Martínez-Calatrava R Gómez R Largo Gabriel Herrero-Beaumont 《Arthritis research & therapy》2013,15(4):R81
Objective
The aim of this study was to determine whether hypercholesterolemia increases articular damage in a rabbit model of chronic arthritis.Methods
Hypercholesterolemia was induced in 18 rabbits by administrating a high-fat diet (HFD). Fifteen rabbits were fed normal chow as controls. Chronic antigen-induced arthritis (AIA) was induced in half of the HFD and control rabbits, previously immunized, by intra-articular injections of ovalbumin. After sacrifice, lipid and systemic inflammation markers were analyzed in blood serum. Synovium was analyzed by Krenn score, multinucleated cell counting, immunohistochemistry of RAM11 and CD31, and TNF-α and macrophage chemoattractant protein-1 (MCP-1) gene expression. Active bone resorption was assessed by protein expression of receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and quantification of cathepsin K, contact surface and the invasive area of pannus into bone.Results
Rabbits receiving the HFD showed higher total serum cholesterol, HDL, triglycerides and CRP levels than rabbits fed a normal diet. Synovitis score was increased in HFD, and particularly in AIA and AIA + HFD groups. AIA + HFD synovium was characterized by a massive infiltration of RAM11+ cells, higher presence of multinucleated foam cells and bigger vascularization than AIA. Cathepsin K+ osteoclasts and the contact surface of bone resorbing pannus were also increased in rabbits with AIA + HFD compared with AIA alone. Synovial TNF-α and MCP-1 gene expression was increased in AIA and HFD rabbits compared with healthy animals. RANKL protein expression in AIA and AIA + HFD groups was higher compared with either HFD or normal groups.Conclusions
This experimental model demonstrates that hypercholesterolemia increments joint tissue damage in chronic arthritis, with foam macrophages being key players in this process. 相似文献163.
164.
D H Adams M Hathaway J Shaw D Burnett E Elias A J Strain 《Journal of immunology (Baltimore, Md. : 1950)》1991,147(2):609-612
In addition to its activities as a growth factor, recent studies suggest an immunoregulatory role for transforming growth factor-beta (TGF-beta). In this context we have demonstrated that TGF-beta is a potent chemotactic factor in vitro for human T lymphocytes at a concentration of 40 fM and for monocytes at a concentration of 0.4 fM but that it has no chemotactic activity for neutrophils. Furthermore, using an assay of lymphocyte subset chemotaxis we have been able to show that TGF-beta can induce migration of both CD4+ and CD8+ T lymphocytes in vitro. This study provides further evidence that TGF-beta acts as a cytokine, being able to attract T lymphocytes and monocytes to sites of inflammation. Its role in the pathogenesis of inflammatory reactions is likely to be complex. 相似文献
165.
166.
Laura Sheard Nat MJ Wright Clive E Adams Nicole Bound Bruno Rushforth Roger Hart Charlotte NE Tompkins 《Trials》2009,10(1):1-5
Many research-funding agencies now require open access to the results of research they have funded, and some also require that researchers make available the raw data generated from that research. Similarly, the journal Trials aims to address inadequate reporting in randomised controlled trials, and in order to fulfil this objective, the journal is working with the scientific and publishing communities to try to establish best practice for publishing raw data from clinical trials in peer-reviewed biomedical journals. Common issues encountered when considering raw data for publication include patient privacy – unless explicit consent for publication is obtained – and ownership, but agreed-upon policies for tackling these concerns do not appear to be addressed in the guidance or mandates currently established. Potential next steps for journal editors and publishers, ethics committees, research-funding agencies, and researchers are proposed, and alternatives to journal publication, such as restricted access repositories, are outlined. 相似文献
167.
168.
Tracey E Toms Vasileios F Panoulas Holly John Karen MJ Douglas George D Kitas 《Arthritis research & therapy》2009,11(4):R110-10
Introduction
The metabolic syndrome (MetS) may contribute to the excess cardiovascular burden observed in rheumatoid arthritis (RA). The prevalence and associations of the MetS in RA remain uncertain: systemic inflammation and anti-rheumatic therapy may contribute. Methotrexate (MTX) use has recently been linked to a reduced presence of MetS, via an assumed generic anti-inflammatory mechanism. We aimed to: assess the prevalence of the MetS in RA; identify factors that associate with its presence; and assess their interaction with the potential influence of MTX. 相似文献169.
Crosas B Hanna J Kirkpatrick DS Zhang DP Tone Y Hathaway NA Buecker C Leggett DS Schmidt M King RW Gygi SP Finley D 《Cell》2006,127(7):1401-1413
The ubiquitin ligase Hul5 was recently identified as a component of the proteasome, a multisubunit protease that degrades ubiquitin-protein conjugates. We report here a proteasome-dependent conjugating activity of Hul5 that endows proteasomes with the capacity to extend ubiquitin chains. hul5 mutants show reduced degradation of multiple proteasome substrates in vivo, suggesting that the polyubiquitin signal that targets substrates to the proteasome can be productively amplified at the proteasome. However, the products of Hul5 conjugation are subject to disassembly by a proteasome-bound deubiquitinating enzyme, Ubp6. A hul5 null mutation suppresses a ubp6 null mutation, suggesting that a balance of chain-extending and chain-trimming activities is required for proper proteasome function. As the association of Hul5 with proteasomes was found to be strongly stabilized by Ubp6, these enzymes may be situated in proximity to one another. We propose that through dynamic remodeling of ubiquitin chains, proteasomes actively regulate substrate commitment to degradation. 相似文献
170.
Arno Wegkamp Astrid E Mars Magda Faijes Douwe Molenaar Ric CH de Vos Sebastian MJ Klaus Andrew D Hanson Willem M de Vos Eddy J Smid 《Microbial cell factories》2010,9(1):100