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1.
目的建立天仙子药材中东莨菪碱和莨菪碱的高效液相测定方法。方法采用Symmetrix ODS-H色谱柱,以乙腈-0.1%三氟乙酸水(14∶86)为流动相,检测波长210nm,流速1.0mL/min,测定天仙子药材中东莨菪碱和莨菪碱的含量。结果氢溴酸东莨菪碱和硫酸阿托品的线性范围分别为4.02~513.64μg/mL(r=0.999 9)和4.00~512.00μg/mL(r=0.999 8),平均回收率分别为98.41%和98.79%。结论 HPLC法测定准确、可控,能快速、简便地控制天仙子药材的质量。  相似文献   
2.
Rh2 is a rare ginsenoside and there are few reports of its effect on cognition compared with other similar molecules. This study aimed to establish the impact of Rh2 treatment on improving scopolamine (Scop)‐induced memory deficits in mice and illuminate the underlying mechanisms. First, memory‐related behavior was evaluated using two approaches: object location recognition (OLR), based on spontaneous activity, and a Morris water maze (MWM) task, based on an aversive stimulus. Our results suggested that Rh2 treatment effectively increased the discrimination index of the mice in the OLR test. In addition, Rh2 elevated the crossing numbers and decreased the escape latency during the MWM task. Moreover, Rh2 markedly upregulated the phosphorylation of the extracellular signal‐regulated kinase (ERK)‐cAMP response element binding (CREB)‐brain derived neurotrophic factor (BDNF) pathway in the hippocampus. Meanwhile, the administration of Rh2 significantly promoted the cholinergic system and dramatically suppressed oxidative stress in the hippocampus. Taken together, Rh2 exhibited neuroprotective effects against Scop‐induced memory dysfunction in mice. Rh2 activity might be ascribed to several underlying mechanisms, including its effects on modulating the cholinergic transmission, inhibiting oxidative stress and activating the ERK‐CREB‐BDNF signaling pathway. Consequently, the ginsenoside Rh2 might serve as a promising candidate compound for Alzheimer's disease.  相似文献   
3.
目的 阐明改良桃胶的不同配伍(用量、填充剂)对复杂成分均衡释放的影响.方法 以喘平方为模型药,改良桃胶为缓释辅料,采用体外释放度结合HPLC法,测定喘平缓释片的指标成分(麻黄碱、伪麻黄碱、东莨菪碱)释放度,计算累积释放曲线斜率(K)值,评价指标成分间是否均衡释放.结果 不同配伍考察中,当填充剂为淀粉、淀粉/糊精、淀粉/微晶纤维素(MCC)时,各指标成分K值接近,实现了均衡释放;而与糊精、MCC配伍时,K值差异较大,无法均衡释放.随着改良桃胶辅料用量的增加,释药时间延长,指标成分的K值基本一致,达到均衡释放.结论 不同填充剂与改良桃胶配伍,会影响中药复方缓释制剂复杂成分的均衡释放;不同处方用量的改良桃胶,会影响药物的释放时间,但不影响其均衡释放.  相似文献   
4.
目的:研究孟鲁司特(Mon)对东莨菪碱(Scop)致痴呆模型小鼠学习记忆及脑内胆碱能神经的影响。方法:将动物按体重随机分为5组,正常对照组[溶媒(Veh)+Veh]、阴性对照组(Scop+Veh)、阳性对照组[Scop+多奈哌齐(Done)2.0mg/kg]、低剂量孟鲁司特组(Scop+Mon 1.0mg/kg)、高剂量孟鲁司特组(Scop+Mon2.0mg/kg)。灌胃给药,除正常对照组腹腔注射生理盐水外,其他各组小鼠给药前30min腹腔注射东莨菪碱(1.0mg·kg^-1·d^-1),连续给药14d后采用Morris水迷宫和Y迷宫实验测定学习记忆功能,并测定脑海马及皮层乙酰胆碱(ACh)水平及乙酰胆碱酯酶(TChE)的活性。结果:与阴性对照组相比,孟鲁司特(1.0、2.0mg·kg^-1·d^-1)能显著缩短Morris水迷宫隐藏平台训练的潜伏期,增加动物在空间探索实验中对目标象限的搜索时间及原平台所在位置的穿越次数,增加Y迷宫实验中正确反应次数。孟鲁司特还能显著降低小鼠海马及皮层乙酰胆碱酯酶活性,增加乙酰胆碱含量。结论:孟鲁司特通过抑制东莨菪碱所致的痴呆小鼠脑内乙酰胆碱酯酶活性增加乙酰胆碱含量,继而改善小鼠学习记忆损害。  相似文献   
5.
目的:观察东莨菪碱对氯胺酮依赖者焦虑障碍的治疗效果。方法:对30例氯胺酮依赖者焦虑障碍给予东莨菪碱治疗,采用 HAMA 量表评价出院时,出院1、3月后的治疗效果。结果:治疗后患者焦虑症状消失,情绪明显改善,对氯胺酮的渴求明显减弱或消失。结论:东莨菪碱治疗氯胺酮依赖者焦虑障碍具有一定的疗效。  相似文献   
6.
目的:观察覆盆子不同提取部位对东莨菪碱、亚硝酸钠及40%乙醇造成的小鼠记忆障碍模型的影响,探索覆盆子对这3种记忆障碍模型的有效部位,为进一步研究覆盆子对学习记忆改善作用的机制提供依据。方法:昆明种小鼠130只,随机分成13组,每组10只。即正常组,模型组,阳性组,覆盆子全药高剂量和低剂量组,三氯甲烷部位高剂量和低剂量组,正丁醇部位高剂量和低剂量组,乙酸乙酯部位高剂量和低剂量组,水提部位高剂量和低剂量组。给药组小鼠分别以高、低剂量(24,12 g·kg~(-1))ig覆盆子全药、三氯甲烷部位、正丁醇部位、乙酸乙酯部位、水提部位;阳性药组给银杏叶制剂量为7.6 mg·kg~(-1),正常组和模型组给予等量的蒸馏水,连续12 d。7 d后除正常组外,东莨菪碱所致模型测试前30 min ip 1 mg·kg~(-1),亚硝酸钠所致模型训练后ip 120 mg·kg~(-1),40%乙醇所致模型测试前30 min ig 0.1 m L·kg~(-1),检测小鼠在Morris水迷宫的定位航行能力和空间探索能力。结果:与正常组比较,3种记忆障碍逃避潜伏期明显延长,穿越平台次数明显缩短(P0.05);与模型组比较,覆盆子全药、三氯甲烷部位、正丁醇部位、乙酸乙酯部位、水提部位均可缩短3种记忆障碍逃避潜伏期,增加其穿越平台次数(P0.05)。结论:覆盆子水提部位高剂量组对东莨菪碱、亚硝酸钠造成的小鼠记忆障碍模型改善效果最优;覆盆子全药高剂量组对40%乙醇造成的记忆障碍小鼠模型改善效果最优。  相似文献   
7.
Short-term oestradiol treatment modulates hippocampus-dependent memory and synaptic plasticity in the hippocampus. Long-term oestradiol treatment can also enhance hippocampus- dependent memory, although the effects of long-term oestradiol treatment on synaptic plasticity are unknown. We investigated the effects of long-term oestradiol treatment on synaptic plasticity at the Schaeffer Collateral/CA1 synapse in 8-month-old female rats. In addition, we determined the role of endogenous activation of muscarinic acetylcholine receptors (mAChRs) in synaptic transmission and plasticity using scopolamine (1 μm), an antagonist of mAChRs. Hippocampus slices from ovariectomised rats that were treated with oestradiol-containing capsules for 5 months were compared with slices from ovariectomised rats that received cholesterol-containing capsules. Unexpectedly, scopolamine application significantly increased the baseline field excitatory postsynaptic potentials (fEPSP) and decreased paired pulse facilitation (PPF) in slices from cholesterol-treated rats. Baseline fEPSPs and PPF were not significantly modulated in slices from oestradiol-treated rats by scopolamine. Slices from oestradiol-treated rats showed enhanced long-term potentiation relative to slices from cholesterol-treated rats. Scopolamine significantly reduced the magnitude of plasticity in slices from oestradiol-treated rats. Taken together, these results suggest that mAChRs have a significant effect on baseline synaptic transmission through a decrease in the probability of glutamate release in slices from cholesterol-treated rats. Long-term oestradiol treatment blocks this effect and enhances theta-burst stimulation-induced synaptic plasticity in the middle-aged female rat, and this effect is mediated by activation of mAChRs.  相似文献   
8.
More effective countermeasures against nerve‐agent poisoning are needed, because current ones do not protect sufficiently, particularly the central nervous system (CNS). The purpose of the present study was to make a comparison of the antidotal capabilities of atropine/obidoxime/diazepam (termed the obidoxime regimen), atropine/HI‐6 (1‐[([4‐(aminocarbonyl)pyridinio]methoxy)methyl]‐2‐[(hydroxyimino)methyl]pyridinium)/avizafone (termed the HI‐6 regimen), and scopolamine/HI‐6/physostigmine (termed the physostigmine regimen) against various doses of soman (2, 3, 4 x LD50). The results showed that each regimen administered twice (1 min and 5 min after exposure) effectively prevented or terminated epileptiform activity within 10 min. However, the regimens differed markedly in life‐saving properties with the physostigmine regimen ranking highest followed in descending order by the HI‐6 and obidoxime regimens. Pretreatment with pyridostigmine increased the potency of the HI‐6 regimen, but not the obidoxime regimen. The latter regimen administered thrice (1 min, 5 min, and 9 min after exposure) did not compensate for the insufficiency. In half of the rats that lived for 7 days, neuropathology was unexpectedly observed predominantly in the left hemisphere unrelated to whether they seized or not. Local glutamatergic excitotoxic activity may occur even if manifest toxic signs are absent. The physostigmine regimen has excellent antidotal capacity, but the very narrow therapeutic window (< 10 min) makes it unsuitable for use in the field. The HI‐6 regimen appears to constitute an efficacious therapy against lower doses of soman (2 and 3 x LD50). Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   
9.
目的 观察垂体后叶素对东莨菪碱致小鼠认知功能障碍的影响.方法 健康昆明种小鼠48只,随机分为4组:正常组(Con组)、东莨菪碱组(Sco组)、东莨菪碱+垂体后叶素大剂量组(Sco+Pit 30 U/kg组)、东莨菪碱+垂体后叶素小剂量组(Sco+Pit 3.0 U/kg组),每组12只.腹腔注射东莨菪碱1 mg/kg制备认知功能障碍模型,用跳台和避暗实验观察垂体后叶素对东莨菪碱致小鼠认知功能障碍的影响.结果 与Con组相比,Sco组小鼠在跳台实验与避暗实验中的潜伏期均缩短,错误次数均增加(P〈0.05);与Sco组相比,Sco+Pit组小鼠在跳台实验与避暗实验中的潜伏期均延长,错误次数均减少(P〈0.05).结论 垂体后叶素可减轻东莨菪碱致小鼠认知功能障碍.  相似文献   
10.

Background and Purpose

Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors.

Experimental Approach

E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R''s effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion.

Key Results

Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084''s stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity.

Conclusion and Implications

E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases.  相似文献   
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