全文获取类型
收费全文 | 205篇 |
免费 | 5篇 |
专业分类
210篇 |
出版年
2020年 | 2篇 |
2019年 | 6篇 |
2017年 | 1篇 |
2016年 | 3篇 |
2015年 | 7篇 |
2014年 | 6篇 |
2013年 | 14篇 |
2012年 | 11篇 |
2011年 | 8篇 |
2010年 | 7篇 |
2009年 | 8篇 |
2008年 | 15篇 |
2007年 | 6篇 |
2006年 | 9篇 |
2005年 | 5篇 |
2004年 | 7篇 |
2003年 | 5篇 |
2002年 | 4篇 |
2001年 | 8篇 |
2000年 | 1篇 |
1999年 | 3篇 |
1998年 | 3篇 |
1997年 | 3篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 2篇 |
1993年 | 1篇 |
1992年 | 7篇 |
1991年 | 3篇 |
1990年 | 5篇 |
1988年 | 1篇 |
1987年 | 2篇 |
1986年 | 7篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1981年 | 2篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1971年 | 5篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1968年 | 2篇 |
1967年 | 1篇 |
1966年 | 2篇 |
1965年 | 1篇 |
排序方式: 共有210条查询结果,搜索用时 0 毫秒
61.
62.
Structural information regarding binding of peptides to the major histocompatibility complex (MHC) class II molecule is of great use for the design of compounds that intervene in the interaction between the MHC-peptide-T-cell receptor (TCR) complex. These compounds can be applied in the treatment of T-cell-mediated auto-immune disease for specific modulation of the disease process. In case no crystal structure of the MHC molecule is available, homology models of the MHC molecule can be of importance. Here we describe the construction of a homology model of the MHC class II molecule and binding of the peptide, that are involved in experimental auto-immune encephalomyelitis, a rat model for human multiple sclerosis. The validity of the model was investigated using experimental data of peptides binding to this MHC molecule. 相似文献
63.
Laras Y Garino C Dessolin J Weck C Moret V Rolland A Kraus JL 《Journal of enzyme inhibition and medicinal chemistry》2009,24(1):181-187
Synthesis and enzymatic evaluation of new series of N(4)-substituted piperazine naphthamide derivatives as BACE-1 inhibitors for the treatment of Alzheimer's disease are reported. 相似文献
64.
Rolland A Boquet I Norreel JC Moret V Laras Y Kraus JL 《Bioorganic & medicinal chemistry letters》2008,18(1):169-174
Using SVZ (subventricular zone) tissue explants from one-day-old mice, we investigated the activity of new amino aromatic disulfide analogues and polyazamacrocycles on the migration of SVZ cells (neuroblasts). We found that among the tested analogues, non-peptidic disulfide derivative 8 significantly decreases the migration of neuroblasts from SVZ cells, and antagonized the stimulating activity of disulfide cyclic peptide 1. Discovery of compounds 1 and 8 constitutes new chemical tools which could be used to understand the mechanism of neuroblast migration during neurogenesis and eventually to identify specific genes involved in the neurogenesis. 相似文献
65.
Here we characterized transepithelial taurine transport in monolayers of cultured human intestinal Caco-2 cells by analyzing kinetic apical and basolateral uptake and efflux parameters. Basolateral uptake was Na+- and Cl−- dependent and was inhibited by β-amino acids. Uptake by this membrane showed properties similar to those of the apical TauT system. In both membranes, taurine uptake fitted a model consisting of a non-saturable plus a saturable component, with a higher half-saturation constant and transport capacity at the apical membrane (Km, 17.1 μmol/L; Vmax, 28.4 pmol·cm−2·5 min−1) than in the basolateral domain (Km, 9.46 μmol/L; Vmax, 5.59 pmol·cm−2·5 min−1). The non-saturable influx component, estimated in the absence of Na+ and Cl−, showed no significant differences between apical and basolateral membranes (KD, 89.2 and 114.7 nL·cm−2 · 5 min−1, respectively). Taurine efflux from the cells is a diffusive process, as shown in experiments using preloaded cells and in trans-stimulation studies (apical KD,72.7 and basolateral KD, 50.1 nL·cm−2·5 min−1). Basolateral efflux rates were significantly lower than passive influx rates. We conclude that basolateral taurine uptake in Caco-2 cells is mediated by a transport mechanism that shares some properties with the apical system TauT. Moreover, calculation of unidirectional and transepithelial taurine fluxes reveals that apical influx of this amino acid is higher than basolateral efflux rates, thereby enabling epithelial cells to accumulate taurine against a concentration gradient. 相似文献
66.
The balance between Cu,Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. 总被引:13,自引:0,他引:13
P Amstad A Peskin G Shah M E Mirault R Moret I Zbinden P Cerutti 《Biochemistry》1991,30(38):9305-9313
Oxidants are toxic, but at low doses they can stimulate rather than inhibit the growth of mammalian cells and play a role in the etiology of cancer and fibrosis. The effect of oxidants on cells is modulated by multiple interacting antioxidant defense systems. We have studied the individual roles and the interaction of Cu,Zn-superoxide dismutase (SOD) and catalase (CAT) in transfectants with human cDNAs of mouse epidermal cells JB6 clone 41. Since only moderate increases in these enzymes are physiologically meaningful, we chose the following five clones for in-depth characterization: CAT 4 and CAT 12 with 2.6-fold and 4.2-fold increased catalase activities, respectively, SOD 15 and SOD 3 with 2.3-fold and 3.6-fold increased Cu,Zn-SOD activities, respectively, and SOCAT 3 with a 3-fold higher catalase activity and 1.7-fold higher Cu,Zn-SOD activity than the parent JB6 clone 41. While the increases in enzyme activities were moderate, the human cDNAs were highly expressed in the transfectants. As demonstrated for the clone SOD 15, this discordance between message concentrations and enzyme activities may be due to the low stability of the human Cu,Zn-SOD mRNA in the mouse recipient cells. According to immunoblots the content of Mn-SOD was unaltered in the transfectants. While the activities of glutathione peroxidase were comparable in all strains, the concentrations of reduced glutathione (GSH) were significantly lower in SOD 3 and SOD 15. This decrease in GSH may reflect a chronic prooxidant state in these Cu,Zn-SOD overproducers.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
67.
Y. Laras C. Garino J. Dessolin C. Weck V. Moret A. Rolland 《Journal of enzyme inhibition and medicinal chemistry》2013,28(1):181-187
Synthesis and enzymatic evaluation of new series of N4-substituted piperazine naphthamide derivatives as BACE-1 inhibitors for the treatment of Alzheimer's disease are reported. 相似文献
68.
L A Pinna A Donella G Clari V Moret 《Biochemical and biophysical research communications》1976,70(4):1308-1315
The partial purification of a rat liver cytosol protein phosphatase is described, resulting in a preparation active on casein but not on phosvitin, cytosol phosphopeptides, ATP, ADP and p-nitrophenylphosphate, which, on the contrary, are still dephosphorylated by the protein phosphatase purified from rat liver mitochondria. Moreover the activity of the former enzyme on casein appears to involve only a limited amount of phosphoric sites which are also preferentially phosphorylated by soluble protein kinase. The isolation and evaluation of 32P-serine and 32P-threonine from protein-kinase-dependently labelled phosvitin and casein, before and after incubation with the two enzymes, led to the conclusion that mitochondrial protein phosphatase hydrolyzes more actively the phosphorylserine residues, while the cytosol “casein phosphatase” promotes a preferential breakdown of the 32P-threonine residues. 相似文献
69.
Both cytosol and mitochondria of rat liver display protein kinase activity, cyclic AMP-independent, which is resolved by Sepharose 6B filtration and P-cellulose chromatography into multiple forms phosphorylating, besides endogenous mitochondrial membrane-bound proteins, also exogenous phosphoproteins such as casein and phosvitin. However, the forms by far predominant in the cytosol phosphorylate both phosphorylserine and phosphorylthreonine residues of casein, while most of the activity associated to mitochondrial structures is due to the forms phosphorylating only phosphorylserine residues. 相似文献
70.
Involvement of cellular cyclic AMP in theophylline-induced sugar accumulation in chicken intestinal epithelial cells 总被引:1,自引:0,他引:1
We have studied the possible involvement of cellular cyclic AMP in theophylline-induced sugar gradient enhancement in isolated chicken enterocytes. Theophylline increases 3-O-methylglucose accumulation 3-fold after 30 min incubation. Exogenous cyclic AMP enhances sugar accumulation by 48%. Adenylyl cyclase inhibitor RMI 12 330A reduces theophylline-induced sugar gradients by 22% and theophylline-induced cyclic AMP levels by 24.5%. At the concentration used, RMI 12 330A has no effect on 3-O-methylglucose accumulation or basal cellular cyclic AMP. Since theophylline has a rapid inhibitory effect on Na+-independent sugar permeability, we conclude that the effects of the drug on sugar gradients are the result of its acting by both direct - surface membrane - and indirect - cyclic AMP mediated - mechanisms. The effect of theophylline and exogenous cyclic AMP on sugar accumulation is independent of external chloride. 相似文献