全文获取类型
收费全文 | 11641篇 |
免费 | 795篇 |
国内免费 | 261篇 |
出版年
2023年 | 161篇 |
2022年 | 203篇 |
2021年 | 396篇 |
2020年 | 382篇 |
2019年 | 425篇 |
2018年 | 504篇 |
2017年 | 319篇 |
2016年 | 327篇 |
2015年 | 406篇 |
2014年 | 799篇 |
2013年 | 825篇 |
2012年 | 540篇 |
2011年 | 780篇 |
2010年 | 570篇 |
2009年 | 587篇 |
2008年 | 545篇 |
2007年 | 661篇 |
2006年 | 507篇 |
2005年 | 390篇 |
2004年 | 318篇 |
2003年 | 344篇 |
2002年 | 297篇 |
2001年 | 174篇 |
2000年 | 151篇 |
1999年 | 163篇 |
1998年 | 136篇 |
1997年 | 136篇 |
1996年 | 129篇 |
1995年 | 115篇 |
1994年 | 115篇 |
1993年 | 105篇 |
1992年 | 101篇 |
1991年 | 100篇 |
1990年 | 59篇 |
1989年 | 49篇 |
1988年 | 37篇 |
1987年 | 50篇 |
1986年 | 37篇 |
1985年 | 94篇 |
1984年 | 101篇 |
1983年 | 56篇 |
1982年 | 76篇 |
1981年 | 60篇 |
1980年 | 79篇 |
1979年 | 53篇 |
1978年 | 55篇 |
1977年 | 38篇 |
1976年 | 35篇 |
1975年 | 33篇 |
1974年 | 39篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
101.
The contribution of the alternative pathway to the respiration of suspension-cultured pear ( Pyrus communis cv. Passa Crasanne) cells was enhanced, often severalfold, within 2 to 4 days following the addition of cycloheximide, actinomycin D, or 2-(4-methyl-2,6-dinitroanalino)- N -methyl propionamide (D-MDMP). Concomitant inhibition of cellular protein synthesis by cycloheximide and actinomycin D was transient and incomplete. However, inhibition by D-MDMP was virtually complete (>97%) and persisted over several days. [35 S]-labelling and polyacrylamide gel separation indicated that cycloheximide precluded the appearance of discernable new proteins in mitochondria. Probes with monoclonal antibodies revealed a conservation of alternative oxidase protein levels in the mitochondria of inhibitor-treated cells. The data, appraised within the complexities of cell-culture dynamics, lead to the conclusion that the observed increases in capacity for cyanide-resistant respiration are the consequence, likely indirect, of inhibited protein synthesis with resultant retention and activation of constitutive alternative oxidase. 相似文献
102.
Harald H. O. Schmid Patricia C. Schmid Viswanathan Natarajan 《Chemistry and physics of lipids》1996,80(1-2):133-142
Long-chain N-acylethanolamines (NAEs) elicit a variety of biological and pharmacological effects, Anandamide (20:4n-6 NAE) and other polyunsaturated NAEs bind to the cannabinoid receptor and may thus serve as highly specific lipid mediators of cell signalling. NAEs can be formed by phospholipase D-catalyzed hydrolysis of N-acylethanolamine phospholipids or by direct condensation of ethanolamine and fatty acid, So far, most of the latter biosynthetic activity has been shown to be the reverse reaction of the NAE amidohydrolase that catalyzes NAE degradation. Thus, increasing evidence supports the hypothesis that the N-acylation-phosphodiesterase pathway yields not only saturated-monounsaturated NAEs, but polyunsaturated ones, including anandamide, as well. 相似文献
103.
Oscar Varela Patricia A. Zunszain Daniel O. Cicero Ricardo F. Baggio Daniel R. Vega María T. Garland 《Carbohydrate research》1996,280(2):187
The conformation in 2H2O of 4-thio-l-lyxono-1,4-lactone (1) was studied by nuclear magnetic resonance spectroscopy, by means of homonuclear (J1H,1H) and heteronuclear (J1H,13C) coupling constants. The couplings were directly measured by a two-dimensional heteronucleus-coupled ω1 hetero-half-filtered proton-proton correlation (HETLOC) experiment, which does not require 13C isotopic enrichment. In solution, the thiolactone ring of 1 adopts preferentially the E3 conformation, and its hydroxymethyl group populates mainly the gt rotamer. The X-ray diffraction data of a single crystal of 1 indicates that also in the solid state the thiolactone ring adopts an E3 conformation, with a puckering somewhat larger than that observed for aldono-1,4-lactones and furanose rings. The molecules are linked by hydrogen bonds, which form chains. Particularly, O-5 is fully engaged as donor and acceptor in hydrogen bonding and the rotameric conformation of the hydroxymethyl group of 1 is fixed in the tg form. 相似文献
104.
M. A. Lelu K. Klimaszewska G. Pflaum C. Bastien 《In vitro cellular & developmental biology. Plant》1995,31(1):15-20
Summary Cotyledonary somatic embryos ofLarix × leptoeuropaea that developed after various maturation times on media containing abscisic acid showed different frequencies of conversion
into plants. Drying of these somatic embryos under high relative humidity (RH) before germination improved plantlet recovery
and eliminated differences in the performance of somatic embryos matured for different times. However, dehydration of somatic
embryos under 98% RH to a water content below that of zygotic embryos excised from mature seeds (0.97 and 1.36 g H2O/g dry weight, respectively) showed a strong positive correlation between longer maturation time and desiccation tolerance.
Drying somatic embryos at 4° C under 59% RH for 1 wk resulted in desiccation to a water content of 0.30 g H2O/g dry weight, which was the closest to the hydration state of zygotic embryos in dried, stored seeds (0.20 g H2O/g dry weight). Under this condition, only somatic embryos matured for 5 wk germinated and produced plantlets at a relatively
high frequency (73 and 41%, respectively). 相似文献
105.
Shigenobu Umeki 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1995,110(4)
The effects of gentamycin on the NADPH oxidase (EC 1.6.99.6) from human neutrophils in both whole-cell and fully soluble (cell-free) systems were investigated. Gentamycin was found to inhibit, concentration-dependently, the superoxide generation of neutrophils exposed to phorbol myristate acetate in a whole-cell system and the activation of superoxide-generating NADPH oxidase by sodium dodecyl sulfate in a cell-free system. The concentrations of the drug required for 50% inhibition of the oxidase (IC50) were 150 μM in the whole-cell system and 10 μM in the cell-free system. In addition, in the cell-free system, the drug did not change the Km value for NADPH of the oxidase. However, gentamycin did not the superoxide generation of NADPH oxidase after its activation in the cell-free system, suggesting that the drug do not have superoxide-scavenger action. These results suggest that gentamycin, an aminoglycoside antibiotic, may exhibit an anti-inflammatory action due to inhibition of neutrophil NADPH oxidase activation. 相似文献
106.
Harjit S. Minhas Paul J. Thornalley 《Journal of biochemical and molecular toxicology》1995,10(5):245-250
Repletion of depleted cellular reduced glutathione (GSH) levels in oxidative stress and exposure to arylating agents is a strategy for the development of antidotes to chemical toxicity. The effect of GSH, reduced glutathione ethyl monoester (GSHEt), and reduced glutathione ethyl diester (GSHEt2) on the cytotoxicity of hydrogen peroxide, 1-chloro-2,4-dinitrobenzene (CDNB), and menadione to P388D1 macrophages in vitro was investigated. The median toxic concentration TC50 values of the toxicants were hydrogen peroxide 24 ± 2 mM (N = 19), CDNB 63 ± 6 μM (N = 18), and menadione 30 ± 4 μM (N = 22). Reduced glutathione, GSHEt, and GSHEt2 were poor antidotes to hydrogen peroxide toxicity. Indeed, the observed antidote effects were attributed to the nonenzymatic reaction of the GSH derivatives with hydrogen peroxide in the extracellular medium. Reduced glutathione ethyl diester was a more potent antidote of CDNB- and menadione-mediated toxicity than GSHEt and GSH. For cell incubations with the approximate median toxic concentration TC50 values of hydrogen peroxide, CDNB, and menadione, the respective median effective antidote concentration EC50 values were GSHEt 23.8 ± 4.1 mM (N = 9), 3.6 ± 0.6 mM (N = 11), and 226 ± 93 μM (N = 12); and GSHEt2 20.4 ± 1.9 mM (N = 6), 603 ± 2 μM (N = 9), and 7.6 ± 2.3 μM (N = 12). Reduced glutathione ethyl diester was a potent antidote to CDNB- and menadione-induced toxicities but not to hydrogen peroxide-induced toxicity under acute intoxication conditions. © 1996 John Wiley & Sons, Inc. 相似文献
107.
Xiao-Ming Zhou Patricia Curran Jesse Baumgold Peter H. Fishman 《Journal of neurochemistry》1994,63(4):1361-1370
Abstract: Exposure of human SK-N-MC neurotumor cells to 4β-phorbol 12-myristate 13-acetate (PMA) increased isoproterenol stimulation of cyclic AMP levels by severalfold. This potentiation was blocked by inhibitors of protein kinase C (PKC) and did not occur in cells in which PKC had been down-regulated. PMA treatment also enhanced the stimulation by dopamine, cholera toxin, and forskolin. Thus, the effect of PMA on the adenylylcyclase system was postreceptor and involved either the guanine nucleotide binding regulatory (G) proteins or the cyclase itself. As PMA treatment did not impair the inhibition of isoproterenol stimulation by neuropeptide Y, an involvement of the inhibitory G protein Gi was unlikely. Cholate extracts of membranes from control and PMA-treated cells were equally effective in the reconstitution of adenylylcyclase activity in S49 cyc? membranes, which lack the stimulatory G protein subunit Gsα; thus, Gs did not appear to be the target of PMA action. Membranes from PMA-treated cells exhibited increased adenylylcyclase activity to all stimulators including Mn2+ and Mn2+ plus forskolin. In addition, activity was increased when control membranes were incubated with ATP and purified PKC from rat brain. This is consistent with a direct effect of PKC on the adenylylcyclase catalyst in SK-N-MC cells. PMA treatment also resulted in a shift to less sensitivity in the Kact for isoproterenol but not for dopamine or CGP-12177 (a β3-adrenergic agonist) stimulation. Thus, the β1 but not the D1 or β3 receptors were being desensitized by PKC activation. Analysis of SK-N-MC cells by western blotting with antibodies against different PKC isozymes revealed that both the α and ζ isozymes were present in these cells. Whereas PKC-α was activated and translocated from cytosol to membrane by phorbol esters, the ζ isozyme was not. Thus, PKC-α, which has been implicated in desensitization in other cell lines, also appears to potentiate adenylylcyclase activity. 相似文献
108.
Abstract: Effects of ascorbic acid (AA) on 125 I-SCH 23982 binding to D1 dopaminergic receptors in membrane preparations from rat striatum were investigated. AA in the range of 0.03 µ M –0.33 m M inhibited 75% of specific binding of 125 I-SCH 23982 in a dose-dependent manner. At higher concentrations, this inhibition of binding activity by AA was less potent, and 3.3 m M AA inhibited only 30% of specific binding. Reduced glutathione did not alter the inhibition of binding by 0.33 m M AA, but reduced the inhibition by 3.3 m M AA to 8% of specific binding. The loss of specific binding by AA was rescued by 1 m M EDTA, an inhibitor of lipid peroxidation. In the absence of AA, competition experiments with the agonist, dopamine, revealed the presence of high-affinity ( K h = 224.9 ± 48.9 n M ) and low-affinity ( K l = 21,100 ± 2,400 n M ) binding sites. Although the maximum binding of 125 I-SCH 23982 decreased to 40% without affecting the K D value in the presence of 1.67 m M AA, the value of the high-affinity site for dopamine was increased ( K h = 23.3 ± 9.4 n M ) and that of the low-affinity site was decreased ( K l = 136,800 ± 40,900 n M ). These results suggest that AA may affect D1 dopamine receptor function by lipid peroxidation, competition with dopamine for low-affinity sites, and reduced oxidation of dopamine. 相似文献
109.
Gordon Y. K. Ng †Brian F. O'Dowd ‡Mirelle Caron ‡Michael Dennis §Mark R. Brann † Susan R. George 《Journal of neurochemistry》1994,63(5):1589-1595
Abstract: We have expressed and biochemically characterized the human D2long (D2L ) dopamine receptor isoform using the baculovirus/Sf9 cell system. The expressed receptor bound ligands with a pharmacological profile similar to that reported for neuronal and cloned D2L receptors expressed in mammalian cell lines. Dopamine binding to D2L receptor was sensitive to guanine nucleotides, indicating receptor coupling to endogenous G proteins. A D2L receptor-specific antibody identified two major protein species at ∼44 kDa and at ∼93 kDa in immunoblots, suggesting the presence of D2L receptor monomers and dimers. Both species were purified by immunoprecipitation from digitonin-solubilized preparation of cells expressing D2L receptor prelabeled with 32 Pi or [3 H]-palmitate. These results constitute the first direct evidence for D2L receptor phosphorylation and palmitoylation. 相似文献
110.
Abstract: Solubilization of rat striatal membranes with sodium cholate, followed by reconstitution into phospholipid vesicles, leads to a 6.5-fold increase in the agonist high-affinity binding sites of the D1 dopamine receptor. These high-affinity binding sites display differential sensitivity toward temperature. When reconstituted receptors were preincubated for 1 h at 0–4°C (on ice) or at 22°C (room temperature) followed by radioligand binding assays with dopamine, neither the high-affinity values of the receptor for dopamine nor the percent receptors in the high-affinity state (31–39%) were changed from control reconstituted receptors, which were not subject to any preincubations. At 30°C, there was a partial loss in the number of high-affinity D1 receptors with only 25% of the total receptor population in the high-affinity state; there was no change in the affinity values of the high-affinity binding sites. At 37°C, there was a 40% loss in total number of D1 receptor binding sites. All the high-affinity binding sites were lost and the remaining 60% of binding activity represented the low-affinity binding state of the receptor. These results indicate that the high-affinity binding sites of the reconstituted D1 dopamine receptors are uniquely sensitive to higher temperatures. 相似文献