全文获取类型
收费全文 | 286篇 |
免费 | 17篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 3篇 |
基础医学 | 30篇 |
口腔科学 | 15篇 |
临床医学 | 13篇 |
内科学 | 11篇 |
皮肤病学 | 5篇 |
神经病学 | 89篇 |
特种医学 | 1篇 |
外科学 | 3篇 |
综合类 | 38篇 |
预防医学 | 1篇 |
眼科学 | 37篇 |
药学 | 62篇 |
中国医学 | 8篇 |
肿瘤学 | 1篇 |
出版年
2023年 | 1篇 |
2022年 | 4篇 |
2021年 | 1篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 6篇 |
2017年 | 6篇 |
2016年 | 3篇 |
2015年 | 8篇 |
2014年 | 9篇 |
2013年 | 17篇 |
2012年 | 16篇 |
2011年 | 15篇 |
2010年 | 20篇 |
2009年 | 14篇 |
2008年 | 19篇 |
2007年 | 14篇 |
2006年 | 18篇 |
2005年 | 17篇 |
2004年 | 10篇 |
2003年 | 9篇 |
2002年 | 8篇 |
2001年 | 6篇 |
2000年 | 6篇 |
1999年 | 4篇 |
1998年 | 3篇 |
1997年 | 7篇 |
1996年 | 8篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 3篇 |
1992年 | 3篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1983年 | 4篇 |
1982年 | 1篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1976年 | 1篇 |
排序方式: 共有318条查询结果,搜索用时 15 毫秒
81.
82.
Daniel J O'Leary Joseph Nazarian Michel Millodot 《Clinical & experimental optometry》1986,69(3):108-111
Corneal sensitivity was assessed before and after applying atropine (0.5, 0.05, 0.005% w/v), pilocarpine (1.0, 0.1%), eserine (0.1, 0.01%) and potassium chloride (171mM). Atropine (0.5 ? 0.005%) significantly depressed corneal sensitivity; parasympathomimetics, taken together, significantly increased sensitivity. Exposure to potassium chloride for 2 min had no effect on sensitivity, nor did it affect corneal sensation. These results are consistent with the hypothesis that epithelial acetylcholine is a neurotransmitter to the corneal nerves. We conclude, however, that the nerves may have only weak muscarinic properties. 相似文献
83.
Oral doses of pilocarpine increase salivary flow rates in patients afflicted with xerostomia (dry mouth). This study examined the pharmacokinetics of and a pharmacodynamic response (salivation) to intravenous pilocarpine nitrate administration in dogs. Disposition was linear over a dose range of 225–600 µg/kg; plasma concentrations were 10–120 µg/L. Elimination was rapid and generally biphasic, with a terminal elimination half-life of approximately 1.3 hr. The systemic clearance of pilocarpine was high (2.22 ± 0.49 L/kg/hr) and its steady-state volume of distribution (2.30 ± 0.64 L/kg) was comparable to that of many other basic drugs. All doses of pilocarpine induced measurable submaxillary and parotid salivary flow rates which could be maintained constant over time. Cumulative submaxillary saliva flow was linearly related to total pilocarpine dose. Plasma pilocarpine concentration was linearly related to both steady-state and postinfusion submaxillary salivary flow rates. 相似文献
84.
癫痫大鼠海马中神经肽Y表达的动态观察及其作用探讨 总被引:3,自引:0,他引:3
目的 探讨癫痫大鼠海马中神经肽 Y( NPY)表达的动态变化及其作用 ,以及外源性 NPY对癫痫的影响。方法 将 SD大鼠随机分为 4组 ,采用匹鲁卡品 ( PILO)癫痫动物模型及外源性 NPY侧脑室注入干预法 ,并以免疫组织化学染色观察 NPY的表达。结果 癫痫模型组 PILO注射后 ,门区、CA3区、CA1 区的 NPY阳性细胞数表达增多 ,1 2 h达高峰 ,以后逐渐下降 ,60 d又达一高峰 ;海马颗粒细胞层有 NPY异位表达 ,3 d时最明显 ;NPY干预组门区 NPY阳性细胞数较其对照组表达少。结论 ( 1 )癫痫发作后急性期海马 NPY表达增多及颗粒细胞层出现异位表达 ,与癫痫发作有关 ;( 2 )外源性 NPY有抗癫痫作用。 相似文献
85.
Ilse Smolders Ghous M Khan Jacqueline Manil Guy Ebinger Yvette Michotte 《British journal of pharmacology》1997,121(6):1171-1179
- Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist.
- Focally evoked pilocarpine-induced seizures in freely moving rats were provoked by intrahippocampal pilocarpine (10 mM for 40 min at a flow rate of 2 μl min−1) administration via a microdialysis probe. Concomitant changes in extracellular hippocampal glutamate, γ-aminobutyric acid (GABA) and dopamine levels were monitored and simultaneous electrocorticography was performed. The animal model was characterized by intrahippocampal perfusion with the muscarinic receptor antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 μM) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine maleate, 100 μM). The effectiveness of locally (600 μM) or systemically (10 mg kg−1 day−1) applied lamotrigine against the pilocarpine-induced convulsions was evaluated.
- Pilocarpine initially decreased extracellular hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced limbic convulsions extracellular glutamate, GABA and dopamine concentrations in hippocampus were significantly increased. Atropine blocked all changes in extracellular transmitter levels during and after co-administration of pilocarpine. All pilocarpine-induced increases were completely prevented by simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801 and lamotrigine resulted in an elevation of hippocampal dopamine levels and protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced convulsions developed in the rats which received lamotrigine perorally.
- Pilocarpine-induced seizures are initiated via muscarinic receptors and further mediated via NMDA receptors. Sustained increases in extracellular glutamate levels after pilocarpine perfusion are related to the limbic seizures. These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.
86.
H. Schwörer K. Racké H. Kilbinger 《Naunyn-Schmiedeberg's archives of pharmacology》1989,339(3):263-267
Summary Isolated small intestinal segments of the guinea pig were arterially perfused and the release of 5-hydroxytryptamine (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) into the portal venous effluent measured by HPLC with electrochemical detection. Test substances were applied via the arterial perfusion medium. McN-A-343, pilocarpine and oxotremorine inhibited concentration-dependently the outflow of 5-HT and 5-HIAA. Pirenzepine (0.03–0.1 mol/l) which can discriminate between M1 and M2-receptor subtypes antagonized completely this inhibitory effect. In the presence of 1 mol/l tetrodotoxin (TTx), all three muscarine receptor agonists increased the outflow of 5-HT and 5-HIAA. Oxotremorine 1 mol/l was most effective and increased the outflow of 5-HT by 145%, that of 5-HIAA by 235%. McN-A-343 and pilocarpine, both at a concentration of 10 mol/l, increased the outflow of 5-HT by about 40%, that of 5-HIAA by 50% and 71%, respectively. The stimulatory effect of oxotremorine was competitively antagonized by pirenzepine; a pA2 value of 7.70 was calculated. In conclusion, the cholinergic modulation of the release of 5-HT from the enterochromaffin cells consists of an indirect inhibitory (via the release of a neurotransmitter) and a direct stimulatory component. Muscarine receptors mediating the indirect effect may belong to the M1-subtype whereas the direct stimulatory effect may be mediated by a mixed population of M1 and M2 receptors or by a subtype of M1 receptors.
Send offprint requests to H. Schwörer at the above address 相似文献
87.
目的 :研究匹罗卡品致痫后大鼠行为、EEG及大脑组织学变化特征。方法 :SD大鼠匹罗卡品腹腔注射 ,诱发急性癫痫持续状态 (SE)后 ,观察慢性期自发性发作 ;描记EEG ;Neo Timm染色观察海马苔藓出芽 ,Nissl染色观察海马神经元损伤。结果 :注射匹罗卡品后 ,87%的动物呈现SE ,持续 6~ 2 4h后这一部分大鼠均出现慢性自发发作 ,组织学检查发现海马有显著的神经元损伤 ,齿状回内分子层苔藓纤维出芽。结论 :匹罗卡品模型基本复制了人类颞叶癫痫的临床病理特征 ;SE所致的海马结构性损伤及苔藓纤维重构是自发性发作形成的基础 相似文献
88.
MDJuan-Manuel Anaya Chief MDNorman Talal Professor of Medicine 《Seminars in arthritis and rheumatism》1999,28(6):355-359
Primary Sjögren's syndrome (SS) is an autoimmune exocrine disease characterized by salivary and lacrimal gland destruction progressing to xerostomia and xerophthalmia (sicca symptoms). Nevertheless, any exocrine as well as nonexocrine organ may be involved. Dryness is not solely a result of glandular destruction; cytokines, autoantibodies, and other soluble factors may be also involved. We propose a two-stage model of SS pathogenesis in which the initial process seems to be increased epithelial cell apoptosis leading to autoantibody production and subsequent salivary gland lymphocytic infiltration. Treatment of SS includes education, prevention, tears and saliva substitution, exocrine glands stimulation, and immunointervention. Pilocarpine, a natural alkaloid and stimulator of muscarinic receptors in exocrine glands, is an effective agent for the treatment of sicca symptoms. Another systemic stimulatory agent to treat sicca symptoms is cevimeline, a quinuclidine derivative of acetylcholine that exhibits high affinity for the muscarinic M3 receptor which is located on lacrimal and salivary gland epithelium. Molecular understanding of the biological mechanisms that lead to tissue damage in SS may lead to newer biological treatment for this common, disabling and at times devastating illness. 相似文献
89.
Mikati MA Rizk E El Dada S Zeinieh M Kurdi R El Hokayem J Rahmeh A Koubeissi M Kobeissi M Azzam D Usta J El Sabban M Dbaibo G 《Brain & development》2008,30(8):513-519
Ceramide is known to induce programmed cell death (PCD) in neural and non-neural tissues and to increase after kainic acid (KA) status epilepticus (SE). Ceramide increases have been shown to depend on NMDA receptor activation in the KA model, but these changes have not been studied in the lithium pilocarpine (LiPC) model. Thus, the purpose of this study was to determine if hippocampal ceramide levels increase after LiPC induced SE and if NMDA receptor blockade prevents PCD and any such ceramide increases. We found that LiPC induced SE resulted in ceramide increases and DNA fragmentation in the hippocampus of adult, P21, and P7 rats. The administration of MK-801, the NMDA receptor antagonist, in adults, 15min prior to pilocarpine, prevented ceramide increases, and DNA fragmentation. 相似文献
90.
Manuela Mazzuferi Eleonora Palma Katiuscia Martinello Francesca Maiolino Cristina Roseti Sergio Fucile Paolo F. Fabene Federica Schio Michele Pellitteri Guenther Sperk Ricardo Miledi Fabrizio Eusebi Michele Simonato 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(7):3180-3185
Refractory temporal lobe epilepsy (TLE) is associated with a dysfunction of inhibitory signaling mediated by GABAA receptors. In particular, the use-dependent decrease (run-down) of the currents (IGABA) evoked by the repetitive activation of GABAA receptors is markedly enhanced in hippocampal and cortical neurons of TLE patients. Understanding the role of IGABA run-down in the disease, and its mechanisms, may allow development of medical alternatives to surgical resection, but such mechanistic insights are difficult to pursue in surgical human tissue. Therefore, we have used an animal model (pilocarpine-treated rats) to identify when and where the increase in IGABA run-down occurs in the natural history of epilepsy. We found: (i) that the increased run-down occurs in the hippocampus at the time of the first spontaneous seizure (i.e., when the diagnosis of epilepsy is made), and then extends to the neocortex and remains constant in the course of the disease; (ii) that the phenomenon is strictly correlated with the occurrence of spontaneous seizures, because it is not observed in animals that do not become epileptic. Furthermore, initial exploration of the molecular mechanism disclosed a relative increase in α4-, relative to α1-containing GABAA receptors, occurring at the same time when the increased run-down appears, suggesting that alterations in the molecular composition of the GABA receptors may be responsible for the occurrence of the increased run-down. These observations disclose research opportunities in the field of epileptogenesis that may lead to a better understanding of the mechanism whereby a previously normal tissue becomes epileptic. 相似文献