全文获取类型
收费全文 | 139篇 |
免费 | 15篇 |
国内免费 | 1篇 |
出版年
2021年 | 3篇 |
2020年 | 1篇 |
2019年 | 1篇 |
2018年 | 1篇 |
2017年 | 5篇 |
2016年 | 6篇 |
2015年 | 6篇 |
2014年 | 5篇 |
2013年 | 4篇 |
2012年 | 7篇 |
2011年 | 7篇 |
2010年 | 9篇 |
2009年 | 8篇 |
2008年 | 11篇 |
2007年 | 6篇 |
2006年 | 3篇 |
2005年 | 2篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 1篇 |
2001年 | 5篇 |
2000年 | 1篇 |
1999年 | 1篇 |
1998年 | 10篇 |
1997年 | 6篇 |
1996年 | 4篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 6篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1990年 | 1篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1987年 | 4篇 |
1986年 | 1篇 |
1985年 | 2篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1977年 | 1篇 |
1975年 | 2篇 |
排序方式: 共有155条查询结果,搜索用时 15 毫秒
91.
D Pennica W J Kohr B M Fendly S J Shire H E Raab P E Borchardt M Lewis D V Goeddel 《Biochemistry》1992,31(4):1134-1141
An expression plasmid encoding the extracellular portion of the human tumor necrosis factor (TNF) type 1 receptor (TNF-R1) was constructed and used to generate a stable cell line secreting soluble TNF-R1 (sTNF-R1). The sTNF-R1 was purified, and its biochemical properties and its interactions with human TNF-alpha were examined. SDS-PAGE resolved the purified sTNF-R1 into three bands of approximate Mr 24,200, 28,200, and 32,800. Sedimentation equilibrium analysis gave a molecular weight of 25,000 for sTNF-R1 whereas the molecular weight obtained by gel filtration chromatography was approximately 55,000-60,000. Scatchard analysis of [125I]TNF-alpha binding to sTNF-R1 revealed high-affinity binding (Kd = 93 pM), comparable to that observed for the intact receptor on whole cells. Competitive binding experiments showed that sTNF-R1 has a 50-60-fold higher affinity for TNF-alpha than for TNF-beta, in contrast to the equal affinities of TNF-alpha and TNF-beta for the full-length TNF-R1 transiently expressed in mammalian cells. The sTNF-R1 was found to block the cytotoxicity of TNF-alpha and TNF-beta on a murine L-M cell assay. The sizes of the sTNF-R1.TNF-alpha complex determined by gel filtration chromatography and sedimentation equilibrium were approximately 141 and 115 kDa, respectively. The stoichiometry of the complex was examined by Scatchard analysis, size-exclusion chromatography, HPLC separation, amino acid composition, sequence analysis, and sedimentation equilibrium. The data from these studies suggest that at least two molecules of sTNF-R1 can bind to a single TNF-alpha trimer.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
92.
Kohr MJ Aponte AM Sun J Wang G Murphy E Gucek M Steenbergen C 《American journal of physiology. Heart and circulatory physiology》2011,300(4):H1327-H1335
S-nitrosylation (SNO) is a reversible protein modification that has the ability to alter the activity of target proteins. However, only a small number of SNO proteins have been found in the myocardium, and even fewer specific sites of SNO have been identified. Therefore, this study aims to characterize potential SNO sites in the myocardium. We utilized a modified version of the SNO-resin-assisted capture technique in tandem with mass spectrometry. In brief, a modified biotin switch was performed using perfused mouse heart homogenates incubated with or without the S-nitrosylating agent S-nitrosoglutathione. Our modified SNO-resin-assisted capture protocol identified 116 unique SNO-modified proteins under basal conditions, and these represent the constitutive SNO proteome. These constitutive SNO proteins are likely to be physiologically relevant targets, since nitric oxide has been shown to play an important role in the regulation of normal cardiovascular physiology. Following S-nitrosoglutathione treatment, we identified 951 unique SNO proteins, many of which contained multiple SNO sites. These proteins show the potential for SNO. This study provides novel information regarding the constitutive SNO proteome of the myocardium, as well as potential myocardial SNO sites, and yields additional information on the SNO sites for many key proteins involved in myocardial contraction, metabolism, and cellular signaling. 相似文献
93.
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94.
95.
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
96.
97.
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98.
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
Background
Using a functional genomics approach we addressed the impact of folate overproduction on metabolite formation and gene expression in Lactobacillus plantarum WCFS1. We focused specifically on the mechanism that reduces growth rates in folate-overproducing cells. 相似文献99.
100.
Mirjam MJ Jacobs Ronald G van den Berg Vivianne GAA Vleeshouwers Marcel Visser Rolf Mank Mariëlle Sengers Roel Hoekstra Ben Vosman 《BMC evolutionary biology》2008,8(1):145