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51.
General anaesthetic actions on ligand-gated ion channels 总被引:15,自引:0,他引:15
The molecular mechanisms of general anaesthetics have remained largely obscure since their introduction into clinical practice
just over 150 years ago. This review describes the actions of general anaesthetics on mammalian neurotransmitter-gated ion
channels. As a result of research during the last several decades, ligand-gated ion channels have emerged as promising molecular
targets for the central nervous system effects of general anaesthetics. The last 10 years have witnessed an explosion of studies
of anaesthetic modulation of recombinant ligand-gated ion channels, including recent studies which utilize chimeric and mutated
receptors to identify regions of ligand-gated ion channels important for the actions of general anaesthetics. Exciting future
directions include structural biology and gene-targeting approaches to further the understanding of general anaesthetic molecular
mechanisms.
Received 10 December 1998; received after revision 22 February 1999; accepted 23 February 1999 相似文献
52.
Yang SJ Huh JW Lee JE Choi SY Kim TU Cho SW 《Cellular and molecular life sciences : CMLS》2003,60(11):2538-2546
Aluminum inactivated glutamate dehydrogenase (GDH) by a pseudo-first-order reaction at micromolar concentrations. A double-reciprocal plot gave a straight line with a kinact of 2.7 min-1 and indicated the presence of a binding step prior to inactivation. The inactivation was strictly pH dependent and a marked increase in sensitivity to aluminum was observed as the pH decreased. At a pH higher than 8.5, no inactivation was observed. The completely inactivated GDH contained 2 mol of aluminum per mole of enzyme subunit monomer. When preincubated with enzyme, several chelators such as citrate, NaF, N-(2-hydroxyethyl) ethylenediaminetriacetic acid or ethylenediaminetriacetic acid efficiently protected the enzyme against the aluminum inactivation. In a related experiment, only citrate and NaF released the aluminum from the completely inactivated aluminum-enzyme complex and fully recovered the enzyme activity. Ferritin, NADP+, or nerve growth factor did not show any effects on the recovery of the aluminum-inactivated GDH activity. The dissociation constant for the aluminum-enzyme complex was calculated to be 5.3 M. Although aluminum has been known to form a complex with nucleotides, no such effects were observed in the inactivation of GDH by aluminum as determined using GDHs mutated at the ADP-binding site, NAD+-binding site or GTP-binding site. Circular dichroism studies showed that the binding of aluminum to the enzyme induced a decrease in helices and sheets and an increase in random coil. Therefore, inactivation of GDH by aluminum is suggested to be due to the conformational change induced by aluminum binding. These results suggest a possibility that aluminum-induced alterations in enzymes of the glutamate system may be one of the causes of aluminum-induced neurotoxicity.Received 25 July 2003; received after revision 27 August 2003; accepted 15 September 2003 相似文献
53.
本文介绍了用海藻酸钙凝胶固定化谷氨酸棒杆菌T_(6-13)原生质体生产谷氨酸脱氢酶GDH,Eel.4.1.4的研究。固定化原生质体培养72h后发酵液中GDH活力可达到1.64×~(-2)U/mL,为游离细胞内产酶的205%.固定化原生质体还可用溶菌酶处理固定化细胞而制得,与直接制得的固定化原生质体具有同样的产酶能力,且制备方便,可重复使用,具有良好的贮藏稳定性。 相似文献
54.
生物节律是指生物在自然选择、长期进化过程中保存下来的适应性表象。谷氨酸(Glu)是中枢神经系统(CNS)中主要的兴奋性氨基酸类神经递质,已经证实谷氨酸含量有近似昼夜节律现象,同时谷氨酸在调节人体生物节律的过程中扮演重要角色。最近的研究发现,择时运动对谷氨酸的含量及近似昼夜节律会产生明显影响,对运动队异地训练和比赛时快速地调整时差、延缓疲劳有重要意义。 相似文献
55.
类产碱假单胞菌的谷氨酸脱氢酶水平受氮源调节,以氮为唯一氮源时酶水平有明显提高,研究表明,该酶的最适反应温度为50℃,催化氢化反应和脱氨反应的最适pH值分别为8.0和8.8,金属离子及嘌呤核苷酸对酶活力的影响不显著。 相似文献
56.
比较观察了在新生期腹腔内注射不同剂量谷氨酸单钠后,成年大鼠16个脑区的神经元损伤程度.发现大多数脑区的神经元显著减少,但有的脑区对谷氨酸单钠的神经毒性具有一定保护作用. 相似文献
57.
D. Chao G. Balboni L. H. Lazarus S. Salvadori Y. Xia 《Cellular and molecular life sciences : CMLS》2009,66(6):1105-1115
Activation of δ-opioid receptors (DOR) attenuates anoxic K+ leakage and protects cortical neurons from anoxic insults by inhibiting Na+ influx. It is unknown, however, which pathway(s) that mediates the Na+ influx is the target of DOR signal. In the present work, we found that, in the cortex, (1) DOR protection was largely dependent
on the inhibition of anoxic Na+ influxes mediated by voltage-gated Na+ channels; (2) DOR activation inhibited Na+ influx mediated by ionotropic glutamate N-methyl-D-aspartate (NMDA) receptors, but not that by non-NMDA receptors, although both played a role in anoxic K+ derangement; and (3) DOR activation had little effect on Na+/Ca2+ exchanger-based response to anoxia. We conclude that DOR activation attenuates anoxic K+ derangement by restricting Na+ influx mediated by Na+ channels and NMDA receptors, and that non-NMDA receptors and Na+/Ca2+ exchangers, although involved in anoxic K+ derangement in certain degrees, are less likely the targets of DOR signal.
Received 26 November 2008; received after revision 26 December 2008; accepted 13 January 2009 相似文献
58.
Glutamate, by activation of metabotropic receptors (mGluRs), can lead to a reduction of synaptic efficacy at many synapses.
These forms of synaptic plasticity are referred to as long-term depression (mGluR-LTD). We will distinguish between mGluR-LTD
induced by pre- or postsynaptic receptors and mGluR-LTD induced by the locus of the expression mechanism of the synaptic depression.
We will also review recent evidence that mGluR-mediated responses themselves are subject to depression, which may constitute
a form of metaplasticity.
Received 13 May 2008; received after revision 07 July 2008; accepted 11 July 2008 相似文献
59.
60.
发酵过程很复杂,不同发酵阶段的控制策略必须随着发酵阶段的变化而相应调整。以往的策略由于发酵过程中伴随的随机干扰的影响未能对发酵阶段做出准确判断而使得在线监控效果不够理想。以移动时间窗为基础,通过对时间窗时段内的变量线性拟合找出变量在当前时段的变化趋势,然后用相关分析找出变化趋势中的拐点,即发酵阶段之间的切换点。以此为基础,通过正常批次各阶段特征的总结及和非正常批次对比、归类,实现对染菌、低产两种非正常批次的在线初步诊断。 相似文献