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141.
W. Lasoń J. Turchan B. Przewłocka D. Łabuz J. Mika R. Przewłocki 《Journal of neural transmission (Vienna, Austria : 1996)》1997,104(2-3):125-133
Summary The expression of mRNA coding for AMPA selective glutamate (Glu) R2 receptor and kainate selective GluR5 receptor was studied in the rat hippocampal formation in two animal models of limbic seizures evoked by systemic administration of pilocarpine (400 mg/kg ip) or kainate (15 mg/kg ip). As shown by an in situ hybridization study, pilocarpine decreased the GluR2 flip mRNA level in CA1 and CA3 areas of the hippocampus after 3h and kainate after 24 h, e.g. at the time preceding neuronal degeneration. No changes in the GluR2 flop or GluR5 mRNA level were found in those regions. In the dentate gyrus, resistant to neurodegeneration, pilocarpine and kainate differentialy affected the expression of GluR2 and GluR5 mRNAs. After 72 h pilocarpine, but not kainate, increased the GluR2 flop mRNA level and decreased the flip one, which suggests attenuation of the GluR2 sensitivity. On the other hand, kainate, elevated the GluR2 flip and GluR5 mRNA level in the dentate gyrus after 72 h. All in all the above data suggest that changes in the GluR2 gene expression may play some role in the neuronal damage to vulnerable areas (CA1, CA3). However, differences in the kainate- and pilocarpine-induced changes in the dentate gyrus at the late time points indicate that alterations in the stoichiometry of GluR2 forms or GluR5 gene expression in this brain region are not a common causal factor responsible for delayed neuronal hyperexcitability. 相似文献
142.
目的 :运用正交试验与调优运算法对硝酸毛果芸香碱滴眼液最佳配方进行优选 ,并对其稳定性进行预测。方法 :选取影响硝酸毛果芸香碱滴眼液稳定性3个主要因素 :pH值、温度和贮存时间 ,每个因素选3个水平 ,按L9(33)正交表安排试验 ,以3个指标评定硝酸毛果芸香碱滴眼液稳定性 ,筛选最稳定因素进行温度加速试验 ,并采用t0 9 法对其稳定性进行预测。结果 :pH为4、温度为8℃、贮存时间为12h为最佳优选点 ;温度加速试验预测其贮存期为76 9d。结论 :用正交与调优运算法对硝酸毛果芸香碱滴眼液稳定性进行预测 ,方法简便、快速、准确 相似文献
143.
本文研究的药膜是在室温条件下将含药的单体放在模具中进行辐射交联聚合。该法工艺简便,药膜纯度高不带任何引发剂残余物。我们研究了基质含水率,药物含量、辐射剂量率及总剂量对药物释放速率的影响。结果表明:药物的释放量随着基质含水率及药含量的增加而增加;随着交联剂用量及辐照剂量率和总剂量的增加而降低。药物在剂量率为6.46×10~3Rad/sec及总剂量为1.28×10~6ad条件下辐照与未经辐照处理的药物进行了红外及紫外对比试验,结果表明;辐照对药物结构没有明显的影响。 相似文献
144.
Ryo Suzuki M.D. H. Yoshino Shunsaku Kobayashi 《Documenta ophthalmologica. Advances in ophthalmology》1988,69(1):73-81
We investigated the effect of pilocarpine on the bovine iris sphincter. This muscle contracted in a dose-dependent manner from 2 × 10–6 M, with a maximal response at 3 × 10–3 M. The ED50 values was (1.6 ± 0.3) × 10–4M. Pilocarpine generated a desensitization while desensitization was not significant in the case of other cholinergic agents such as acetylcholine (Ach) and carbachol. Desensitization was profoundly increased in the presence of Ach, neostigmine or eserine: the responses to the second and third trials of pilocarpine were reduced to approximately 8–10% or 30% of the corresponding first responses. Pilocarpine reportedly releases transmitters and alters choline-acetyltransferase activity.These results taken together suggest that either variable Ach synthesis, inhibitory transmitter release or possible toxic action in high concentrations may be involved in the pilocarpine-induced responses of the bovine iris sphincter muscle. The desensitization and parital agonist-antagonist action of pilocarpine could not explain the characteristics of the bovine iris sphincter muscle. 相似文献
145.
Kristen E Belmonte David B Jacoby Allison D Fryer 《British journal of pharmacology》1997,121(7):1287-1294
- The function of inhibitory neuronal M2 muscarinic receptors in diabetic rat lungs was investigated.
- Neuronal M2 muscarinic receptors inhibit acetylcholine release from parasympathetic nerves. Thus, stimulation of neuronal M2 muscarinic receptors with muscarinic agonists, such as pilocarpine, inhibits acetylcholine release and vagally induced bronchoconstriction. In contrast, blockade of neuronal M2 muscarinic receptors with selective M2 muscarinic antagonists, such as AF-DX 116, potentiates acetylcholine release and vagally induced bronchoconstriction.
- Rats were made diabetic by streptozotocin (65 mg kg−1, i.v.). After 7–14 days the rats were anaesthetized with urethane (1.5 g kg−1, i.p.), tracheostomized, vagotomized, ventilated and paralysed with suxamethonium (30 mg kg−1, i.v.). Some 7 day diabetic rats were treated with low doses of long acting (NPH) insulin (2 units day−1, s.c.) for 7 days before experimentation. This dose of insulin was not sufficient to restore normoglycaemia in diabetic rats. Thus, insulin-treated diabetic rats remained hyperglycaemic.
- Distal electrical stimulation (5–70 Hz, 6 s, 40 V, 0.4 ms) of the vagi caused bronchoconstriction, measured as an increase in inflation pressure and bradycardia. In diabetic rats, vagally induced bronchoconstriction was significantly depressed vs controls. In contrast, bronchoconstriction caused by i.v. acetylcholine was similar in diabetic and control animals.
- The function of neuronal M2 muscarinic receptors was tested with the muscarinic agonist pilocarpine (0.001–100.0 μg kg−1, i.v.) and the antagonist AF-DX 116 (0.01–3.0 mg kg−1, i.v.). Pilocarpine inhibited vagally-induced bronchoconstriction (30 Hz, 20–40 V, 0.4 ms at 6 s) and AF-DX 116 potentiated vagally-induced bronchoconstriction (20 Hz, 20–40 V, 0.4 ms at 6 s) to a significantly greater degree in diabetic rats compared to controls.
- Both frequency-dependent vagally-induced bronchoconstriction and M2 muscarinic receptor function could be restored to nearly control values in diabetic rats treated with low doses of insulin.
- Displacement of [3H]QNB (1 nM) with the agonist carbachol (10.0 nM–10.0 mM) from diabetic cardiac M2 muscarinic receptors revealed a half log increase in agonist binding affinity at both the high and low affinity binding sites vs controls. In contrast, M2 receptors from insulin-treated diabetic rat hearts showed no significant difference in binding affinity vs controls.
- These data show that neuronal M2 muscarinic receptors in the lungs have increased function in diabetic rats, suggesting that insulin modulates M2 muscarinic receptor function.
146.
Ocular Absorption and Irritation of Pilocarpine Prodrug Is Modified with Buffer,Polymer, and Cyclodextrin in the Eyedrop 总被引:1,自引:0,他引:1
Suhonen Pekka Järvinen Tomi Lehmussaari Kari Reunamäki Timo Urtti Arto 《Pharmaceutical research》1995,12(4):529-533
The influence of buffer, viscosity and cyclodextrin on the ocular absorption and irritation of a pilocarpine prodrug, O,O-dipropionyl-(1,4-xylylene) bispilocarpic acid diester, was studied in albino rabbits. The prodrug solutions, equivalent to 0.5% pilocarpine, were prepared in 0, 10, 20, 50, or 75 mM citrate buffer at pH 5.0. Viscosity of the solutions (20, 50 or 115 cP) was modified with hydroxypropyl methylcellulose. 2-hydroxypropyl--cyclodextrin (HPCD) was included at concentrations 5,10 and 15% (w/v). The formulations were compared to a commercial pilocarpine eyedrop (1.7%). Ocular irritation was graded in a double-masked experiment and miosis was used as a bioassay for pilocarpine delivery to the iris. The prodrug showed decreased peak and prolonged duration of miosis compared to pilocarpine, but it caused ocular irritation. Increasing buffer strength decreased and elevated viscosity intensified the miotic response and irritation by the pilocarpine prodrug. HPCD decreased both the ocular delivery of pilocarpine and the irritation by the pro-drug, but the net effect was positive. Thus, administering 1.0% of pilocarpine as a prodrug with 15% (w/v) HPCD, the irritation was at the same level with the commercial pilocarpine eyedrop, but the ocular delivery was substantially improved. In conclusion, the ocular delivery of the pilocarpine prodrug may be enhanced in relation to its local irritation by properly combining buffer, viscosity and HPCD. 相似文献
147.
双侧下丘注射NE或阿托品后,大鼠听源性癫痫发作(audiogenic seizure, AS)显著减弱。注射NE前5分钟,先在双侧下丘注射α_2-NE能受体阻断剂盐酸育亨宾(4μg),1小时后,NE对AS的抑制作用被完全逆转,而未预先注射育亨宾的大鼠的AS易感性仍显著低下。双侧下丘注射毒蕈碱样受体的激动剂毛果芸香碱(10μg)后,AS易感品系中不发作的大鼠表现出AS易感性。 实验结果提示:下丘NE水平的提高减弱AS,NE可能是作用于下丘内与外周α_2-NE能受体相似的受体而抑制AS的。下丘毒蕈碱样受体的激活对AS起促进作用。 相似文献
148.
Rivelilson Mendes de Freitas Fábio de Oliveira Silva Gláucio Barros Saldanha Joaquín Jordán 《Fundamental & clinical pharmacology》2011,25(4):485-492
This study was aimed at investigating the anticonvulsant activity of lipoic acid (LA) against pilocarpine‐induced seizures as well as the effects of this metabolic antioxidant on the hippocampal extracellular concentrations of amino acid neurotransmitters glutamate, aspartate, glycine and glutamate and γ‐aminobutyric acid (GABA). In vivo microdialysis demonstrated that an intraperitoneal administration of pilocarpine induced a pronounced increment of hippocampal glutamate and aspartate concentrations, whereas no significant change was observed in the levels of glycine or GABA. LA (10, 20 or 30 mg/kg) pretreatment completely blocked pilocarpine‐evoked increases in extracellular glutamate and aspartate concentrations. Significant reductions in hippocampal GABA and glycine concentrations were also observed although not as pronounced as those shown by glutamate and aspartate. Based on the finding that LA protected rats against pilocarpine‐induced seizures, it could be suggested that the reduction in inhibitory amino acid neurotransmitters levels was comparatively minor and offset by a more pronounced reduction in glutamate and aspartate extracellular concentrations. Therefore, the fact that LA could drastically reduce pilocarpine‐induced increases in glutamate and aspartate should account, at least partly, for its anticonvulsant activity observed in pilocarpine‐induced seizure in rats. 相似文献
149.
150.
De Fu He ; Dong Liang Ma ; Yong Cheng Tang ; Jerome Engel Jr ; Anatol Bragin ; Feng Ru Tang 《Brain pathology (Zurich, Switzerland)》2010,20(1):80-95
The goal of this study was to examine the morpho-physiologic changes in the dorsal subiculum network in the mouse model of temporal lobe epilepsy using extracellular recording, juxtacellular and immunofluorescence double labeling, and anterograde tracing methods. A significant loss of total dorsal subicular neurons, particularly calbindin, parvalbumin (PV) and immunopositive interneurons, was found at 2 months after pilocarpine-induced status epilepticus (SE). However, the sprouting of axons from lateral entorhinal cortex (LEnt) was observed to contact with surviving subicular neurons. These neurons had two predominant discharge patterns: bursting and fast irregular discharges. The bursting neurons were mainly pyramidal cells, and their dendritic spine density and bursting discharge rates were increased significantly in SE mice compared with the control group. Fast irregular discharge neurons were PV-immunopositive interneurons and had less dendritic spines in SE mice when compared with the control mice. When LEnt was stimulated, bursting and fast irregular discharge neurons had much shorter latency and stronger excitatory response in SE mice compared with the control group. Our results illustrate that morpho-physiologic changes in the dorsal subiculum could be part of a multilevel pathologic network that occurs simultaneously in many brain areas to contribute to the generation of epileptiform activity. 相似文献