全文获取类型
收费全文 | 6137篇 |
免费 | 451篇 |
国内免费 | 1篇 |
出版年
2023年 | 48篇 |
2022年 | 82篇 |
2021年 | 181篇 |
2020年 | 131篇 |
2019年 | 148篇 |
2018年 | 197篇 |
2017年 | 192篇 |
2016年 | 292篇 |
2015年 | 362篇 |
2014年 | 389篇 |
2013年 | 427篇 |
2012年 | 569篇 |
2011年 | 480篇 |
2010年 | 278篇 |
2009年 | 264篇 |
2008年 | 341篇 |
2007年 | 292篇 |
2006年 | 290篇 |
2005年 | 272篇 |
2004年 | 264篇 |
2003年 | 225篇 |
2002年 | 205篇 |
2001年 | 46篇 |
2000年 | 40篇 |
1999年 | 49篇 |
1998年 | 59篇 |
1997年 | 43篇 |
1996年 | 33篇 |
1995年 | 32篇 |
1994年 | 33篇 |
1993年 | 30篇 |
1992年 | 25篇 |
1991年 | 22篇 |
1990年 | 16篇 |
1989年 | 15篇 |
1988年 | 11篇 |
1987年 | 9篇 |
1986年 | 17篇 |
1985年 | 20篇 |
1984年 | 12篇 |
1983年 | 13篇 |
1982年 | 17篇 |
1981年 | 16篇 |
1980年 | 8篇 |
1979年 | 9篇 |
1978年 | 12篇 |
1976年 | 15篇 |
1975年 | 7篇 |
1974年 | 7篇 |
1968年 | 6篇 |
排序方式: 共有6589条查询结果,搜索用时 15 毫秒
71.
Peroxynitrite-Induced Cytotoxicity in PC12 Cells: Evidence for an Apoptotic Mechanism Differentially Modulated by Neurotrophic Factors 总被引:10,自引:1,他引:9
†Alvaro G. Estévez ‡Rafael Radi †Luis Barbeito §Jordan T. Shin §John A. Thompson §# Joseph S. Beckman 《Journal of neurochemistry》1995,65(4):1543-1550
Abstract: Peroxynitrite is a powerful oxidant formed by the near-diffusion-limited reaction of nitric oxide with superoxide. Large doses of peroxynitrite (>2 m M ) resulted in rapid cell swelling and necrosis of undifferentiated PC12 cells. However, brief exposure to lower concentrations of peroxynitrite (EC50 = 850 µ M ) initially (3–4 h) caused minimal damage to low-density cultures. By 8 h, cytoplasmic shrinkage with nuclear condensation and fragmentation became increasingly evident. After 24 h, 36% of peroxynitrite-treated cells demonstrated these features associated with apoptosis. In addition, 46% of peroxynitrite-treated cells demonstrated DNA fragmentation (by terminal-deoxynucleotide transferase-mediated dUTP-digoxigenin nick end-labeling) after 7 h, which was inhibited by posttreatment with the endonuclease inhibitor aurintricarboxylic acid. Serum starvation also resulted in apoptosis in control cells (23%), the percentage of which was not altered significantly by peroxynitrite treatment. Although peroxynitrite is known to be toxic to cells, the present study provides a first indication that peroxynitrite induces apoptosis. Furthermore, pretreatment of cells with nerve growth factor or insulin, but not epidermal growth factor, was protective against peroxynitrite-induced apoptosis. However, both acidic and basic fibroblast growth factors greatly increased peroxynitrite-initiated apoptosis, to 63 and 70%, respectively. Thus, specific trophic factors demonstrate differential regulation of peroxynitrite-induced apoptosis in vitro. 相似文献
72.
Rafael Zapata Angels Navarro Enric I. Canela Rafael Franco Carmen Lluis Josefa Mallol 《Journal of neurochemistry》1997,69(6):2546-2554
Abstract: Identification of A1 adenosine receptors (A1 Rs) in a tumor cell line derived from rat pituitary (GH4 cells) was performed by ligand binding and immunological experiments. Subsequently, the involvement of A1 Rs in the regulation of calcium conductance was studied in these cells. The agonist N 6 -( R )-(2-phenylisopropyl)adenosine ( R -PIA) did not modify the intracellular calcium basal levels, whereas it inhibited the increase produced by 15 m M KCl depolarization. The antagonist 1,3-dipropyl-8-cyclopentylxanthine led to the opening of voltage-dependent cell surface calcium channels in the absence of exogenous KCl. The channels were of the L type because the effect was abolished by calciseptine and by verapamil. These results suggest that endogenous adenosine exerts a tonic inhibitory effect on calcium transport. This was confirmed by the high adenosine concentration found in cell supernatants (up to 1 µ M ) and by the calcium mobilization produced by exogenously added adenosine deaminase. In depolarizing conditions, the calcium peak in the presence of adenosine deaminase was reduced when cells were preincubated with R -PIA, thus suggesting that A1 R activation regulates the intensity of depolarization. These results demonstrate that adenosine is an important regulator of the physiological state of pituitary tumor cells by modulating, in an autocrine manner, the activity of L-type voltage-dependent calcium channels. 相似文献
73.
A new monoclonal antibody (3D3) generated with human respiratory mucins and directed against Lewis determinants 总被引:1,自引:1,他引:0
Nathalie Emery; Palfa Shirley B.; Place Graham; Oriol Rafael; Hall Roderick L.; Roussel Philippe; Lhermitte Michel 《Glycobiology》1995,5(6):563-570
We have prepared a monoclonal antibody (MAb), 3D3, raised againstpurified human respiratory mucins. This antibody recognizedmucins and proteolytically derived glycopeptides. The epitoperecognized by the antibody was destroyed by -L-fucosidase, indicatingthat it was present on the carbohydrate moieties. Structuralspecificity was determined by adsorption on a variety of synthetic,insolubilized oligosaccharides. Several lines of evidence indicatethat the 3D3 MAb reacted strongly with the Lewis (Leb) antigen,but also recognized Lea and Ley determinants. This antibodymight be useful to study mucin secretion. human bronchial mucins Lewis b 相似文献
74.
Rafael Apitz-Castro Alicia De Murciano 《Biochimica et Biophysica Acta (BBA)/General Subjects》1978,544(3):529-539
32P phosphorylation of plasma membranes from human blood platelets, under conditions that closely resemble physiological ones (endogeneous phosphate donors and intact platelets in homologous plasma), result in the incorporation of the label mainly in a membrane glycoprotein of apparently high molecular weight (greater than 400 000). Dibutyryl cyclic AMP, an inhibitor of platelet aggregation, specifically increases the degree of phosphorylation of this glycoprotein. Moreover, it has been found that prostaglandin E1 one of the most potent inhibitors of platelet aggregation which also increases phosphorylation of the same glycoprotein, is significantly more effective than cyclic AMP.Cyclic GMP does not have any apparent effect on platelet aggregation. However, incubation of platelet-rich plasma with both cyclic GMP and cyclic AMP results in a partial recovery of the platelet responsiveness towards ADP-induced aggregation. Coincidently, the degree of phosphorylation of the high molecular weight glycoprotein under these conditions, although still higher than in controls (no nucleotides added), is significantly decreased as compared with cyclic AMP-treated cells. Furthermore, cyclic GMP inhibits the cyclic AMP-dependent protein kinase activity in isolated platelet plasma membranes.These results suggest a central role for this membrane phosphoglycoprotein in the triggering of platelet aggregation and, furthermore, suggest that modulation of its degree of phosphorylation may be exerted through some cyclic AMP/cyclic GMP relationship, which in the basal state might be critical for platelet responsiveness. 相似文献
75.
Luis Rodríguez Teresa Ruiz Julio R. Villanueva Rafael Sentandreu 《Current microbiology》1978,1(1):41-44
The intracellular invertase ofSaccharomyces cerevisiae is mainly found in a soluble form (91–95%), while only minor amounts are found bound to the internal (4–8%) and plasma membranes
(less than 1%). In the processes of derepression or repression, inhibition of RNA or protein synthesis, or in the presence
of 2-deoxy-d-glucose, the levels of the membrane-bound and external activities are modified in a way in which their relation is clear,
while the soluble enzyme does not change at all. These results, together with the fact that the membrane-bound and the external
enzymes are glycoproteins, suggest a precursor-product relationship between the enzymic forms. 相似文献
76.
77.
Judith Huerta-Bahena Rafael Villalobos-Molina J.Adolfo García-Sáinz 《Life sciences》1982,30(20):1757-1762
Cycloheximide, a widely used inhibitor of protein synthesis, stimulates glycogenolysis, gluconeogenesis and ureogenesis in isolated rat hepatocytes. The effects of cycloheximide were compared to those of norepinephrine. Both agents, cycloheximide and norepinephrine, produced slight increases in the levels of cyclic AMP (30% increases) which were blocked by propranolol. Interestingly, it was found that the metabolic actions of norepinephrine and cycloheximide (stimulation of glycogenolysis, gluconeogenesis and ureogenesis) were only slightly diminished by the β adrenergic antagonist propranolol but abolished by the selective α1 adrenergic antagonist prazosin. The ability of cycloheximide to inhibit protein synthesis was not affected by either prazosin or propranolol. It is concluded that the stimulation of glycogenolysis, gluconeogenesis and ureogenesis by cycloheximide in rat hepatocytes, is an effect of the antibiotic independent of its ability to inhibit protein synthesis and that is mediated through activation of α1 adrenoceptors. The adrenergic activity of cycloheximide should be considered when this drug is used as an inhibitor of protein synthesis. 相似文献
78.
Silvia M.C. Dias João B. Fernandes José G.S. Maia Otto R. Gottlieb Hugo E. Gottlieb 《Phytochemistry》1982,21(7):1737-1740
The trunk wood of an Amazonian Aniba (Lauraceae) species contains, besides dillapiol and the benzodioxane-type neolignan eusiderin, four bicyclo(3.2.1)octanoid neolignans. These comprise representatives of the canellin-type: the known methoxycanellin-A and the novel compounds characterized as (1R, 3S, 4S, 5S, 6S, 7R)-1-allyl-4-hydroxy-3, 5-dimethoxy-7-methyl-6-(3′-methoxy-4′, 5′-methylenedioxyphenyl)-8-oxo-bicyclo(3.2.1)octane; (1R, 3S, 4S, 5S, 6S, 7R)-1-allyl-4-hydroxy-3, 5-dimethoxy-7-methyl-6-(3′, 4′, 5′-trimethoxyphenyl)-8-oxobicyclo(3.2.1)octane and (1R, 4R, 5R, 6S, 7R, 8S)-1-allyl-4, 8-dihydroxy-5-methoxy-7-methyl-6-(3′-methoxy-4′,5′-methylenedioxyphenyl)-3-oxobicyclo(3.2.1)octane. 相似文献
79.
Marden A. de Alvarenga Raimundo Braz Fo Otto R. Gottlieb João P. de P. Dias Aderbal F. Magalhães Eva G. Magalhães Gouvan C. de Magalhães Mauro T. Magalhães José G.S. Maia Raquel Marques Anita J. Marsaioli Antônio A.L. Mesquita Anselmo A. de Moraes Alaide B. de Oliveira Geovane G. de Oliveira Gentil Pedreira Sebastião K. Pereira Sonildes L.V. Pinho Celira C. Santos 《Phytochemistry》1978,17(3):511-516
Wood samples, infested by fungi during storage, were shown to contain, besides the known 5-methyl-mellein, additional (3R)-8-hydroxy-3-methyl-3,4-dihydroisocoumarins substituted by 7-methyl, 5-formyl, 5-carboxy, 5-hydroxy, 5-methoxy, 6-methoxy-5-methyl and 6,7-dimethoxy-5-methyl groups, as well as 6-formyl-7-hydroxy-5-methoxy-4-methylphthalide. Several 2-methylchromanones were synthesized in order to show that this class of compounds can be distinguished from 3-methyl-3,4-dihydroisocoumarins by MS. 相似文献
80.
A. Dominguez Rosa M. Varona J. R. Villanueva Rafael Sentandreu 《Antonie van Leeuwenhoek》1982,48(2):145-157
The four temperature-sensitive mutants of Saccharomyces cerevisiae in the cell division cycle defective in cytokinesis (cdc, 3, 10, 11 and 12), have been analyzed with respect to the biosynthesis of the cell wall polymers. After 3 hours of incubation at the non-permissive temperature (37°C) these strains stop growing. The synthesis of glucan, mannan and chitin (wall polymers) level off in a similar time, but glucan, mannan and chitin synthases remained active for at least 4 hours.If the mutants are analyzed by transmission and scanning electron microscopy different pictures emerge. Two of the mutants cdc 10 and cdc 12, after 3 hours of incubation at 37°C present apparently normal cytoplasms and cell wall surfaces with multiple elongated buds. The other two mutants, cdc 3 and cdc 11, present a completely disarranged cytoplasmic content and damage at the level of the plasma membrane is evident.These and other observations, suggest that between the execution points of cdc 3 (0.27) and cdc 10 (0.58), essential processes in the assembly of cell membrane occur.This work was supported in part by a grant from la Comisión de Investigación Científica y Técnica of the Spanish Ministerio de Educación y Ciencia (Project no. 4593-1980). 相似文献