全文获取类型
收费全文 | 616篇 |
免费 | 39篇 |
国内免费 | 1篇 |
出版年
2024年 | 4篇 |
2023年 | 4篇 |
2022年 | 5篇 |
2021年 | 8篇 |
2020年 | 4篇 |
2019年 | 5篇 |
2018年 | 12篇 |
2017年 | 15篇 |
2016年 | 15篇 |
2015年 | 15篇 |
2014年 | 33篇 |
2013年 | 39篇 |
2012年 | 42篇 |
2011年 | 40篇 |
2010年 | 28篇 |
2009年 | 19篇 |
2008年 | 29篇 |
2007年 | 26篇 |
2006年 | 19篇 |
2005年 | 25篇 |
2004年 | 15篇 |
2003年 | 18篇 |
2002年 | 19篇 |
2001年 | 18篇 |
2000年 | 14篇 |
1999年 | 9篇 |
1994年 | 5篇 |
1993年 | 5篇 |
1992年 | 11篇 |
1991年 | 13篇 |
1990年 | 8篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 5篇 |
1985年 | 13篇 |
1984年 | 7篇 |
1983年 | 7篇 |
1981年 | 9篇 |
1980年 | 8篇 |
1978年 | 6篇 |
1976年 | 4篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1972年 | 6篇 |
1971年 | 7篇 |
1969年 | 4篇 |
1968年 | 3篇 |
1967年 | 4篇 |
1966年 | 4篇 |
排序方式: 共有656条查询结果,搜索用时 15 毫秒
21.
Mac-2-binding glycoproteins. Putative ligands for a cytosolic beta-galactoside lectin 总被引:4,自引:0,他引:4
I Rosenberg B J Cherayil K J Isselbacher S Pillai 《The Journal of biological chemistry》1991,266(28):18731-18736
Mac-2, a galactose-binding lectin secretion by activated macrophages, is the major non-integrin laminin-binding protein in these cells. Mac-2 is also expressed by epithelial cells in the intestine and kidney. We wished to identify intestinal glycoproteins other than laminin that have a high affinity for Mac-2 and that could be considered as candidate ligands or partners for this lectin in intestinal epithelium. Certain lines of human colon adenocarcinoma cells produce two Mac-2-binding glycoproteins (M2BP-1 and M2BP-2) that were identified by their avid association with Mac-2 following detergent lysis and immunoprecipitation. These glycoproteins do not share a common epitope with Mac-2, and the interaction between Mac-2 and these proteins is mediated through the carbohydrate-binding domain of Mac-2 and sugar moieties on M2BP-1 and M2BP-2. M2BP-1 (98 kDa) and M2BP-2 (70 kDa) were purified by immunoaffinity chromatography and were specifically eluted with either galactose or lactose. Peptide maps revealed that M2BP-1 and M2BP-2 are structurally related. M2BP-1 is secreted and could conceivably associate with Mac-2 extracellularly. N-terminal sequence analysis of M2BP-2 suggests that these glycoproteins represent a unique subset of candidate ligands for this mammalian beta-galactoside lectin. 相似文献
22.
Guinea pigs were given ascorbic acid orally in two doses; a low and a high dose. The tissue levels of ascorbic acid-2-sulphate was estimated in these animals after 15 days of feeding and a subsequent deprivation period of 15 days. The specific activity of the enzymes ascorbic acid sulphotransferase and ascorbic acid-2-sulphate sulphohydrolase was studied. During higher ascorbic acid intake, the activity of ascorbic acid sulphotransferase was increased, whereas ascorbic acid-2-sulphate sulphohydrolase showed a decreased activity. But when ascorbic acid intake was lowered or ceased, the activity of the above enzymes showed a reverse pattern. Possible reasons for the lack of antiscorbutic activity of ascorbic acid-2-sulphate in guinea pigs is discussed. 相似文献
23.
The metacestode of Taenia solium persists for years in the human central nervous system. As proteolytic enzymes play an important role in the survival of tissues helminths, we examined extracts of T. solium metacestodes for proteolytic activity using 9 synthetic peptide substrates and 3 proteins (hemoglobin, albumin, and immunoglobulin G). The proteolytic enzymes were classified based on their inhibitor profiles. At neutral pH, aminopeptidase(arginine-7-amino-4-trifluoromethylcoumarin) and endopeptidase(benzyloxy-carbonyl-glycine-glycine-arginine-7-amino-4- trifluoromethylcoumarin) substrates were cleaved. Hydrolysis of both substrates was inhibited by chelating agents, which inhibit metalloproteases. Peak activity with both substrates eluted in gel filtration fractions corresponding to a molecular weight of about 104 kDa. Cysteine protease activity was identified, which cleaved benzyloxy-carbonyl-phenylalanine-arginine-7-amino- 4-trifluoromethylcoumarin (Z-Phe-Arg-AFC) and hemoglobin. Cleavage of Z-Phe-Arg-AFC was maximal at acid pH, was stimulated by thiols, and was inhibited by leupeptin and Ep459. Peak cysteine protease activity eluted in gel filtration fractions corresponding to a molecular weight of 32 kDa. Aspartic protease activity was identified by specific inhibition with pepstatin of acid digestion of hemoglobin and immunoglobulin G. Immunoglobulin digestion occurred at acid pH, with preferential degradation of the heavy chain. Upon gel filtration chromatography, the aspartic protease activity eluted as a broad peak with maximal activity at about 90 kDa. No serine protease activity was detected. None of the parasite enzymes digested albumin. Proteolytic enzymes of T. solium may be important for parasite survival in the intermediate host, by providing nutrients and digesting host immune molecules. 相似文献
24.
25.
This study examines the effect of various plasma proteins from man on the spontaneous contractile activity of the rat portal vein. Albumin, gamma-globulin, alpha-globulin, beta-globulin (the major plasma proteins), and immunoglobulin IgG (the major immunoglobulin present in the gamma-globulin fraction) were obtained commercially. Mesenteric portal vein strips were prepared from rats and placed in a physiological salt solution in muscle baths for the measurement of longitudinal mechanical response. Portal veins exposed to albumin or gamma-globulin showed a dose-dependent increase in the spontaneous activity, whereas those exposed to alpha-globulin or alpha- and beta-globulin together showed a dose-dependent inhibition of spontaneous activity. Immunoglobulin IgG produced a dose-dependent increase in the spontaneous activity similar to that of gamma-globulin. The increased spontaneous activity produced by albumin was not prevented by ouabain but was inhibited by phentolamine. Spontaneous contractile activity was stimulated by albumin in the chemically (6-hydroxydopamine) denervated portal vein. These findings indicate that albumin acts in a manner similar to noradrenaline. The increased spontaneous activity caused by gamma-globulin (IgG) was inhibited by ouabain or verapamil. The effect of IgG was not dependent on alpha-adrenergic, cholinergic, histaminergic, serotoninergic, or renin angiotensin systems nor was it affected by removal of the endothelium. These observations may have implications in the pathophysiology of essential hypertension. 相似文献
26.
The interaction in vitro of several sulfated glycosaminoglycans with low density lipoproteins (LDL) has been studied. Chondroitin 6-sulfate and heparin were the only ones to produce turbidity when added to LDL in presence of Ca2+. However, when these two glycosaminoglycans were applied to LDL-affinity columns in presence of Ca2+, only chondroitin 6-sulfate was retained. Partially desulfated chondroitin 6-sulfate was not retained on LDL-affinity column, indicating the relevance of sulfate groups in the binding of LDL. Since chondroitin 4-sulfate and heparin, with a sulfate content respectively equal to and greater than that of chondroitin 6-sulfate, are not retained on LDL-affinity columns, the factors relevant to the binding of LDL are probably the conformation of the glycan in solution and the orientation of its sulfate groups. 相似文献
27.
Rajasekharan P. Pillai Robert E. Lenkinski Ted T. Sakai J.Michael Geckle N.Rama Krishna Jerry D. Glickson 《Biochemical and biophysical research communications》1980,96(1):341-349
The assignment of the paramagnetically shifted resonances of the Fe(II)-bleomycin complex in D2O has been accomplished using the transfer of saturation method. A number of additional resonances arising from labile N protons which are shifted by the metal ion are observed in the 1H spectrum of the complex in H2O. The temperature dependence of the chemical shifts is consistent with the formation of an isolated 1:1 complex, but does not obey either the Curie Law or the Curie-Weiss Law. The magnitude of the shifts suggests that the valeric acid hydroxyl (or carbonyl) group, the α-amino group, the imidazole Nπ, the carbamoyl oxygen, the pyrimidine N1 and/or the secondary amino group may be coordinated to the iron(II). 相似文献
28.
29.
Renuka KandhayaPillai Xiaomeng Yang Tamar Tchkonia George M. Martin James L. Kirkland Junko Oshima 《Aging cell》2022,21(6)
Older age and underlying conditions such as diabetes/obesity or immunosuppression are leading host risk factors for developing severe complications from COVID‐19 infection. The pathogenesis of COVID‐19‐related cytokine storm, tissue damage, and fibrosis may be interconnected with fundamental aging processes, including dysregulated immune responses and cellular senescence. Here, we examined effects of key cytokines linked to cellular senescence on expression of SARS‐CoV‐2 viral entry receptors. We found exposure of human umbilical vein endothelial cells (HUVECs) to the inflammatory cytokines, TNF‐α + IFN‐γ or a cocktail of TNF‐α + IFN‐γ + IL‐6, increased expression of ACE2/DPP4, accentuated the pro‐inflammatory senescence‐associated secretory phenotype (SASP), and decreased cellular proliferative capacity, consistent with progression towards a cellular senescence‐like state. IL‐6 by itself failed to induce substantial effects on viral entry receptors or SASP‐related genes, while synergy between TNF‐α and IFN‐γ initiated a positive feedback loop via hyper‐activation of the JAK/STAT1 pathway, causing SASP amplification. Breaking the interactive loop between senescence and cytokine secretion with JAK inhibitor ruxolitinib or antiviral drug remdesivir prevented hyper‐inflammation, normalized SARS‐CoV‐2 entry receptor expression, and restored HUVECs proliferative capacity. This loop appears to underlie cytokine‐mediated viral entry receptor activation and links with senescence and hyper‐inflammation. 相似文献
30.