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61.
Cross-desensitization Reveals Pharmacological Specificity of Excitatory Amino Acid Receptors in Isolated Hippocampal Neurons 总被引:2,自引:0,他引:2
Ionic currents elicited by excitatory amino acids were studied, using the concentration clamp method, in enzymatically isolated rat hippocampal neurons. Cross-desensitization between the responses to various agonists was applied to separate the activity of two types of receptors, N-methyl-d-aspartate (NMDA) and non-NMDA. NMDA receptors were selectively activated by NMDA, l- and d-aspartate, d-glutamate and quinolinate. Kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate appeared to be selective, and quisqualate relatively less selective non-NMDA agonists, acting on the same receptor type. l-Glutamate, l- and d-homocysteate activated both receptor types. It is supposed that two receptor sites, activation site and desensitization site, control the action of agonists at the non-NMDA receptor. When examined in the cross-desensitization experiments, NMDA and non-NMDA receptors appear to be represented by the two homogeneous and independent receptor populations operating different ionic channels. 相似文献
62.
Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development 总被引:1,自引:0,他引:1
Wistar rat pups were administered either a high dose of lead acetate (400 g lead/g body weight/day) or a low dose (100 g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem. 相似文献
63.
L-Arg-NO通路对大鼠延髓腹面加压区心血管活动的影响及与L-Glu通路的关系 总被引:2,自引:0,他引:2
目的:研究一氧化氮(NO)前体L-精氨酸(L-Arg)单侧微量注入大鼠延髓腹面加压区(VSMp)对动脉血压(AP)、心率(HR)、肾灌流压(PPk)的影响及与L-谷氨酸(L-Glu)升压作用的关系。方法 采用延髓腹外侧部微量注射法,以整体灌流肾为模型观察与NO有关药物对心血管活动的影响。结果 (1)VSMp内微量注入L-Arg(40~100nmol),AP和HR呈剂量依赖性下降,与生理盐水注入后的变化相比较,差异均有显著性。如预先注入NO合酶抑制剂L-硝基-精氨酸甲酯(L-NAME)或鸟苷酸环化酶抑制剂甲基蓝,L-Arg的降压效应被衰减。(2)VSMp内微量注入L-Arg(100nmol),PPk与AP同步下降,与基础值比较,差异有显著性。(3)VSMp内微量注入L-Glu(350nmol),AP上升。如预先注 相似文献
64.
观察清开灵对脑组织中谷氨酸 (Glu)和γ 氨基丁酸 (GABA)含量及NMDA受体的数目、亲和力的影响。结果发现 ,清开灵对脑组织中Glu ,GABA含量及Glu GABA值无明显影响 (P >0 .0 5 ) ;能明显下调神经细胞膜上NMDA受体的数目 (P <0 .0 5 )。提示清开灵的脑保护机制与下调NMDA受体的数目有关 相似文献
65.
Elizabeth C Akam Alan M Carruthers Stefan R Nahorski R A John Challiss 《British journal of pharmacology》1997,121(6):1203-1209
- The activation of G proteins by type 1α metabotropic glutamate receptors (mGluRs) in membranes from recombinant baby hamster kidney cells expressing the cloned rat mGluR1α receptor has been studied by use of a [35S]-guanosine 5′-[γ-thio]triphosphate ([35S]-GTPγS) binding assay.
- L-Glutamate increased the rate of [35S]-GTPγS binding in a concentration-dependent manner (−logEC50 (M) 5.25±0.07), with an optimal (62.4±1.6%) increase over basal binding being observed following 60 min incubation at 30°C with 70 pM [35S]-GTPγS, 1 μM GDP, 10 mM MgCl2, 100 mM NaCl and 100 μg membrane protein ml−1. The L-glutamate (100 μM)-stimulated increase in [35S]-GTPγS binding was totally prevented in the presence of the group I mGluR antagonist (S)-4-carboxy-3-hydroxyphenylglycine (300 μM).
- Quantitative analysis of the affinity and number of G proteins activated by a maximally effective concentration of L-glutamate revealed an equilibrium dissociation constant (KD) for [35S]-GTPγS binding of 0.76±0.20 nM and a maximal number of GTPγS-liganded G proteins (Bmax) of 361±30 fmol mg−1 protein.
- Metabotropic glutamate receptor agonists, quisqualate (−logEC50 (M) 6.74±0.06), 1S,3R-ACPD (4.64±0.08) and (S)-3,5-dihydroxyphenylglycine (5.16±0.23) also increased [35S]-GTPγS binding in a concentration-dependent manner, with the latter two agents behaving as partial agonists.
- (+)-α-Methylcarboxyphenylglycine (300 μM) caused a parallel rightward shift of the L-glutamate concentration-effect curve for [35S]-GTPγS binding, allowing an antagonist equilibrium dissociation constant (KD) of 34.0±7.8 μM to be calculated for this mGluR antagonist.
- Pretreatment of BHK-mGluR1α cells with a concentration of pertussis toxin (PTX) shown to be maximally effective (100 ng ml−1, 24 h) before membrane preparation resulted in a marked decrease in agonist-stimulated [35S]-GTPγS binding (by 66.0±0.9%), and an altered concentration-effect relationship for agonist-stimulated [35S]-GTPγS binding by the residual PTX-insensitive G-protein population.
- The modulation of [35S]-GTPγS binding by agonists and antagonists in membranes from recombinant cells provides an excellent system in which to study mGluR interactions with PTX-sensitive and -insensitive G proteins.
66.
J. Jolkkonen P. Jenner C. D. Marsden 《Journal of neural transmission (Vienna, Austria : 1996)》1995,10(2-3):187-198
Summary The mRNA levels encoding enkephalin and substance P were measured in the rat striatum following cortical ablation, blockade of N-methyl-D-aspartate (NMDA) receptors or inhibition of glutamate release by lamotrigine. Unilateral ablation of the cerebral cortex resulted in a decrease of substance P mRNA levels particularly in the rostral dorsolateral and dorsomedial striatum ipsilateral to the lesion. There was a similar trend for a reduction in levels of enkephalin mRNA. Continuous, intrastriatal infusion of the competitive NMDA receptor antagonist, 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, (CPP, 0.12 and 1.2g/day) decreased both enkephalin mRNA and substance P mRNA in dose-dependent manner evenly throughout the striatum adjacent to the infusion site. Following subchronic administration of the presumed glutamate release inhibitor, lamotrigine (5 and 20 mg/kg IP) there was no significant alterations in either enkephalin mRNA or substance P mRNA levels in the striatum. Both enkephalin mRNA and substance P mRNA expression in the rat striatum appear tonically stimulated through postsynaptic NMDA receptor mediated mechanisms. This contrasts with differential dopaminergic modulation of peptides in striatal output neurons. 相似文献
67.
Non-synaptic release may be the major route of excitatory amino acid (EAA) efflux during cerebral ischemia. Possible routes of non-synaptic release include non-specific anion channels, reversal of Na+-, CI?-, or Ca2+-dependent uptake, and cell lysis. In the present study we employ a novel approach to show reversal of Na+-dependent uptake as a major route of EAA efflux from astrocyte cultures under conditions of energy failure. Primary rat astrocyte cultures were subjected to combined blockade of glycolytic and oxidative metabolism after incubation with [3H]-D-aspartate (D-ASP). Energy failure produced an efflux of D-ASP that was maximal by 90 minutes. The efflux over this period was reduced by more than 50% in cells that had been pre-loaded with PDC (L-transpyrrolidine-2,4-dicarboxylic acid) or TBHA (threo-β-hydroxyaspartic acid), compounds that are competitive inhibitors of Na+-dependent glutamate uptake. The effect of pre-loading with the inhibitors was concentration dependent. No effect was seen if the inhibitors were added after induction of energy failure, suggesting that the attenuation of D-ASP efflux resulted from binding of the inhibitors to an intracellular site. These results provide strong evidence that EAA efflux from astrocytes under conditions of energy failure occurs largely through reversal of Na+-dependent uptake. © 1995 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. 相似文献
68.
Intracellular calcium signals triggered by glutamate receptor activation were studied in primary cortical oligodendrocyte lineage cells and in the oligodendrocyte cell line CG-4. Glutamate, kainate, and AMPA (30-300 μM) increased [Ca 2+]i in both types of cells at the stage of oligodendrocyte progenitors (O-2A; GD3+) or pro-oligodendroblasts (04+). The peak amplitude of Ca2+ responses to glutamate receptor agonists was significantly larger in cortical cells. In CG-4 and in cortical cells, the majority (more than 90%) of bipolar GD3+ or multipolar 04+ cells responded to kamate. In all the cells analyzed, kainate was more efficacious than AMPA and glutamate. The percentage of bipolar or multipolar cells responding to glutamate was significantly lower in the CG-4 cell line than in primary cultures. Cellular responses typical of metabotropic glutamate receptor activation were observed in 20% of the cortical O-2A progenitors, but in none of the CG-4 cells. The AMPA-selective antagonist GYKI 52466 blocked kainate-induced Ca2+ responses in cortical O-2A cells. The selective AMPA receptor modulator cyclothiazide (30 μM) greatly potentiated the effects of AMPA (30-100 μM) on [Ca 2+]i in cortical and CG-4 cells. Our findings indicate that Ca2+ responses in cells of the oligodendrocyte lineage are primarily shaped by functional AMPA receptors. © 1995 Wiley-Liss, Inc. 1 This article is a US Government work and, as such, is in the public domain in the United States of America. 相似文献
69.
采用免疫细胞化学双重标记方法研究了雌性大鼠延髓和脊髓内雌激素受体(ER)和代谢型谷氨酸受体1亚型(mGluR1)的分布与共存,以探讨在受体水平神经与内分泌的相互关系。结果发现:链霉亲和素ABC法显示ER免疫反应产物呈棕色,mGluR1免疫反应产物呈蓝黑色。ER和mGluR1在脊髓和延髓有广泛的分布:在脊髓的颈、胸、腰段,ER分布于腹角、背角和侧角;mGluR1的分布与ER相似,但以腹角和背角较为丰富。在延髓,ER分布于舌下神经核、迷走神经背核、三叉神经脊束核、孤束核和网状结构;mGluR1的分布与ER相似,但在数量上有差别。此外,在延髓和脊髓ER和mGluR1广泛共存于许多神经细胞内,即存在着双标细胞。结果提示:雌激素和谷氨酸可通过共存于同一神经细胞的受体,进而在信使、基因和转录水平相互作用,调节神经细胞的机能活动 相似文献
70.
为研究镁在脑缺血早期对神经元保护作用的机制,用电凝法建立大鼠大脑中动脉缺血模型,在造模前给大鼠注射20g/L硫酸镁,观察镁对脑组织中谷氨酸(Glu)及一氧化氮(NO)含量的影响。结果显示,高浓度镁可明显降低脑缺血皮质中Glu、NO含量,在缺血组Glu、NO的峰值浓度分别为9.87、44.97nmol/g,而在加镁组两者浓度分别为7.68、33.92nmol/g。提示:镁对脑缺血早期神经元的保护作用与其降低脑组织中Glu及NO含量有关。 相似文献