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52.
Cantarella G Di Benedetto G Pezzino S Risuglia N Bernardini R 《Journal of neurochemistry》2008,105(5):1915-1923
Tumor necrosis factor related apoptosis inducing ligand (TRAIL) is involved in amyloid beta dependent neurotoxicity via the extrinsic pathway. Recently, several genes modulating TRAIL cytotoxicity have been characterized, providing evidence for a role of wingless-type mouse mammary tumor virus integration site family (Wnt), Jun-N-terminal kinase and other pathways in increased cell susceptibility to the cytokine. We investigated whether neurotoxic effects of TRAIL could be due to modulation of the Wnt signaling pathway. Western blot analysis of Wnt in SH-SY5Y human neuroblastoma cells showed significantly decreased Wnt expression in cultures treated with TRAIL. Correspondingly, both phosphorylation of glycogen synthase kinase 3 beta and degradation of cytoplasmic β-catenin were increased, as well as phosphorylation of the τ protein, bringing about the picture of neuronal damage. As a counterproof of the interaction of TRAIL with the Wnt pathway, the addition of the specific glycogen synthase kinase 3 beta inhibitor SB216763 resulted in rescue of a significant percent of cells from TRAIL-induced apoptosis. The rescue was total when the caspase 8 inhibitor z-IETD-FMK was added in combination with SB216763. Results show that, probably, in addition to triggering caspase signaling, TRAIL also interferes with the Wnt pathway, additionally concurring to neuronal damage. These data suggest that the Wnt pathway substantially contributes to the TRAIL-related neurotoxicity and indicate the TRAIL system as a candidate target for pharmacological treatment of Alzheimer's disease and related disorders. 相似文献
53.
Ferritins are a class of iron storage protein spheres found mainly in the liver and spleen, which have attracted many research interests due to their unique structural features and biological properties. Recently, ferritin and apoferritin (ferritin devoid of the iron core), have been employed as chemically addressable nanoscale building blocks for functional materials development. However, the reactive residues of apoferritin or ferritin have never been specified and it is still unclear about the chemoselectivity of apoferritin towards different kinds of bioconjugation reagents. In this work, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry combined with enzymatic digestion analysis was used to identify the reactive lysine residues of horse spleen apoferritin when conjugated with N-hydroxysuccinimide reagents. The result demonstrated that among all the lysine residues, K97, K83, K104, K67 and K143 are the reactive ones that can be addressed. 相似文献
54.
Dose-dependent neurotoxic effects (decrease in the amplitude of field potentials generated by neurons of the СА1 area, dentate gyrus, and dorsal striatum, but not by neurons of layers ІІ and ІІІ of the parietal cortex, recorded in slices
of the rat brain) were observed 24 h after i.p. injection оf dexamethasone in doses of 7 and 20 mg/kg. Dexamethasone-induced
decreases in the reactivity of glutamatergic synapses in the studied cerebral structures were weakened by a noncompetitive
blocker of NMDA receptors, ketamine (30 mg/kg), and an inhibitor of tyrosine protein phosphatases, sodium vanadate (15 mg/kg),
if the latter agent was injected 6 h after dexamethasone administration. The neurotoxic effect of dexamethasone was intensified
by a coagonist of NMDA receptors, glycine (50 mg/kg), as well as in the case where injections of dexamethasone were combined
with single injections of the antidepressant fluoxetine (20 mg/kg) but not when another antidepressant, pyrazidol, was injected
in the same dose. Chronic (two weeks) injections of fluoxetine and pyrazidol weakened manifestations of dexamethasone neurotoxicity.
On-regulation of NMDA receptors and suppression of expression of neurotrophins are considered probable mechanisms underlying
neurotoxicity of this hormone. The effect of chronic injections of antidepressants on the respective processes is discussed.
Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 312–231, July–August, 2008. 相似文献
55.
Synthetic modeling of tyrosinase (o-phenol ring hydroxylation) has emerged as a novel class of successful biomimetic studies. It is a well-established fact that the reaction of dioxygen with copper(I) complexes of m-xylyl-based ligands generate putative copper-oxygen intermediate species such as side-on peroxo {CuII2(mu-O2)}2+ [in some cases bis-oxo {CuIII2(mu-O)2}2+ in equilibrium with isomeric side-on peroxo], due to oxygen activation. Electrophilic attack of such species brings about monooxygenase activity by incorporating one of the oxygens to m-xylyl ring of the ligand and the other oxygen is reduced to hydroxide ion. The goal of this review is to provide a concise overview of the present day knowledge in this field of research to emphasize the important role the designed ligands play in eliciting the desired tyrosinase-like chemistry. 相似文献
56.
Alain Boissy Jacques Bouix Pierre Orgeur Pascal Poindron Bernard Bibé Pierre Le Neindre 《遗传、选种与进化》2005,37(5):381-401
A total of 1347 weaned lambs from eight genotypes were tested over five consecutive years: Romanov (ROM) and Lacaune (LAC) pure breeds, the two F1 crossbreeds (RL and LR) and the offspring of ewes from these four genotypes sired with Berrichon-du-Cher rams (BCF). The lambs were individually exposed to three challenging tests involving novelty, human contact and social isolation. Ten synthetic variables were used to express social reactivity (i.e., active vs. passive strategy), exploratory activity and reactivity to humans. BCF crossbreds were more active (i.e., high bleats, locomotion and attempts to escape) than purebreds and F1. In contrast, ROM expressed more passive responses (i.e., low bleats and vigilance postures) than LAC and BCF crossbreds. In addition, ROM approached a motionless human less and had longer flight distances to an approaching human than did LAC and BCF crossbreds. When restrained, ROM, and to a lesser extent B×ROM and B×LR, avoided human contact more than did LAC, RL and B×LAC. Most of these differences were explained by direct additive genetic effects while maternal influences or heterosis effects were rarely significant. The highest heritability was for high bleats (h2 = 0.48). Females were more active and avoided human contact more than did males. 相似文献
57.
58.
Shen JS Edwards NJ Hong YB Murray GJ 《Biochemical and biophysical research communications》2008,369(4):1071-1075
Intravenous enzyme replacement therapy (ERT) with purified glucocerebrosidase (GLA) leads to significant improvement of the clinical manifestations in patients with Type 1 Gaucher disease. However, the high doses required, slow response and inability to recover most of the infused enzyme in the target tissues may be attributed to losses occurring during transit en route to the lysosome. Preincubation of GLA with isofagomine (IFG), a slow-binding inhibitor, significantly increased stability of the enzyme to heat, neutral pH and denaturing agents in vitro. Preincubation of GLA with isofagomine prior to uptake by cultured cells results in increased intracellular enzyme activity accompanied by an increase in enzyme protein suggesting that reduced denaturation of GLA in the presence of isofagomine leads to a decrease in the degradation of the enzyme after internalization. Preincubation of GLA with slow-binding inhibitors before infusion may improve the effectiveness of ERT for Gaucher disease. 相似文献
59.
紫菀属化学成分及药理活性研究进展 总被引:5,自引:0,他引:5
紫菀属所含化学成分主要是三萜皂甙 ,此外还含其它萜类、肽类、香豆素、甾醇等 ;其中一些成分具有抗瘤 ,抗菌 ,消炎等活性。本文对其近 2 0多年来国内外学者分离到的化学成分及其药理活性的研究结果作一综述 ,为该属植物资源的进一步研究和开发提供参考。 相似文献
60.
Attilio Converti Adriana Del Borghi Raffaella Gandolfi Alessandra Lodi Francesco Molinari Emilio Palazzi 《Biotechnology and bioengineering》2002,77(2):232-237
The reactivity and thermostability of a novel mycelium-bound carboxylesterase from lyophilized cells of Aspergillus oryzae are explored in organic solvent. Ethanol acetylation was selected as reference esterification reaction. High carboxylesterase activity cells were used as biocatalyst in batch esterification tests at 12.5 < S(o) < 125 mmol L(-1), 5.0 < X(o) < 30 g L(-1), 0.49 < log P < 4.5 and 30 < T < 80 degrees C, as well as in residual activity tests after incubation at 40 < T < 90 degrees C. The starting rates of product formation were used to estimate with the Arrhenius model the apparent activation enthalpies of the enzymatic reaction (29-33 kJ mol(-1)), the reversible unfolding (56-63 kJ mol(-1)), and the irreversible denaturation (22 kJ mol(-1)) of the biocatalyst. 相似文献