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91.
O. Gefvert M. Bergström B. Långström T. Lundberg L. Lindström R. Yates 《Psychopharmacology》1998,135(2):119-126
Quetiapine (Seroquel) is a novel antipsychotic with an atypical profile in animal models and a relatively short plasma half-life
of 2.5–5 h. In the present study, we used PET to compare the time course of blockade of dopamine D2 and serotonin 5HT2 receptors of quetiapine using C11-raclopride and C11-N-methyl-spiperone as ligands, parallel to monitoring plasma drug concentrations. It was an open study in 11 schizophrenic
men using a fixed dose of 450 mg quetiapine. Eight men completed the 29 days treatment, followed by four PET scans performed
over a 26-h period after withdrawal of the compound. Quetiapine was shown to bind to dopamine D2 receptors in striatum and 2 h (tmax) after the last dose, 44% receptor occupancy was calculated. After 26 h it had dropped to the same level as was found in
untreated healthy volunteers. Serotonin 5HT2 receptor blockade in the frontal cortex was 72% after 2 h, which declined to 50% after 26 h. The terminal plasma half-life
of quetiapine was 5.3 h. Clinically, our eight patients had good antipsychotic effect without any extrapyramidal side-effects.
Our data shows that quetiapine has a relatively low affinity for dopamine D2 receptors, with an occupancy half-life (10 h), which was about twice as long as that for plasma. A more prolonged blockade
of the serotonin 5HT2 receptors was found in the frontal cortex, with receptor occupancy half-life of 27 h. Compared to clozapine, as demonstrated
in other studies, quetiapine has much the same ratio of D2/5HT2 occupancy. This could suggest that the combination of D2/5HT2 receptor blockade contributes to the antipsychotic effect and a low incidence of EPS seen with quetiapine in comparative
phase three trials. Our results also confirm the clinical data that quetiapine can be administered twice daily.
Received: 13 December 1996/Final version: 13 June 1997 相似文献
92.
目的观察六味安神胶囊治疗失眠症的疗效。方法将105例患者随机分为2组,六味安神胶囊组(治疗组)60例,对照组45例,2组均连续治疗观察6周。结果治疗组和对照组总有效率分别为91.66%和84.22%,两组疗效差异有显著性意义(P〈0.05)。患者治疗6周后失眠、焦虑等症状较治疗前明显减轻;治疗后及随访时,两组患者匹慈堡睡眠质量指数评分中睡眠质量、入睡时间、睡眠效率、日间功能等因子及总分积分均较治疗前明显下降,差异有统计学意义(P〈0.01),治疗组睡眠障碍积分治疗后与治疗前比较明显降低(P〈0.01)。失眠患者脑干中的5一羟色胺合成减少,治疗组在随访观察时5一羟色胺水平明显高于对照组(P〈0.01)。结论六味安神胶囊用于消除失眠、心律失常、易汗、口干、少津、健忘等症状,优于常用化学催眠药物。 相似文献
93.
This study examined the effect of the acute and chronic administration of the 5-HT(2B/2C) receptor antagonist N-(1-methyl-5-indolyl)-N'-(3-pyridyl) urea hydrochloride (SB-200646A) on the activity of spontaneously active DA cells in the substantia nigra pars compacta (SNC) and ventral tegmental area (VTA) in anesthetized, male Sprague-Dawley rats. This was accomplished using in vivo extracellular single cell recording. The i.v. administration of 4-16 mg/kg of SB-200646A significantly increased the firing rate and % events as bursts in spontaneously active VTA DA neurons and significantly increased the % events as burst in SNC DA neurons. The acute i.p. administration of 20 and 40 mg/kg of SB-200646A significantly increased the number of spontaneously active VTA DA neurons when compared with vehicle-treated controls. The acute administration of 10 mg/kg of SB-200646A significantly increased the coefficient of variation in spontaneously active SNC and DA neurons when compared with vehicle-treated controls. However, the acute i.p. administration of 20 mg/kg of SB-200646A significantly decreased the degree of bursting of VTA DA neurons. Similary, chronic i.p. administration of 10 mg/kg of SB-200646 did not significantly alter firing, whereas chronic administration of 20 mg/kg of SB-200646A or 20 mg/kg of clozapine significantly decreased the number of spontaneously active VTA DA neurons when compared with vehicle-treated controls. The SB-200646A-induced decrease in the number of spontaneously active VTA DA neurons was reversed by the i.v. administration of (+)-apomorphine or (-)-baclofen. The chronic i.p. administration of either 10 or 20 mg/kg of SB-200646A did not significantly alter the firing pattern of spontaneously active SNC DA neurons. However, the chronic administration of 20 mg/kg of SB-200646A significantly increased the degree of bursting in VTA DA neurons when compared with vehicle. Overall, the acute and chronic administration of SB-200646A produces in vivo electrophysiological effects, resembling that of atypical antipsychotic drugs. 相似文献
94.
R. Nitschke N. Benning S. Ricken J. Leipziger K.-G. Fischer R. Greger 《Pflügers Archiv : European journal of physiology》1997,434(4):466-474
In this study we examined the influence of intracellular pH (pHi) on agonist-induced changes of intracellular Ca2+ activity ([Ca2+]i) in HT29 cells. pHi and [Ca2+]i were measured microspectrofluorimetrically using BCECF and fura-2, respectively. Buffers containing trimethylamine (TriMA),
NH3/NH4
+ and acetate were used to clamp pHi to defined values. The magnitudes of the peak and plateau of [Ca2+]i transients induced by carbachol (CCH, 10–6 mol/l) were greatly enhanced by an acidic pHi and nearly abolished by an alkaline pHi. The relationship between pHi and the [Ca2+]i peak was nearly linear from pHi 7.0 to 7.8. This effect of pHi was also observed at higher CCH concentrations (10–4 and 10–5 mol/l), at which the inhibitory effect of an alkaline pHi was more pronounced than the stimulatory effect of an acidic pHi. An acidic pHi shifted the CCH concentration/response curve to the left, whereas an alkaline pHi led to a rightward shift. The influence of pHi on [Ca2+]i transients induced by neurotensin (10–8 mol/l) or ATP (5 × 10–7 mol/l) was similar to its influence on those induced by CCH, but generally not as pronounced. Measurements of cellular inositol
1,4,5-trisphosphate (InsP
3) showed no changes in response to acidification with acetate (20 mmol/l) or alkalinization with TriMA (20 mmol/l). The InsP
3 increase induced by CCH was unaltered at an acidic pHi, but was augmented at an alkaline pHi. Confocal measurements of cell volume showed no significant changes induced by TriMA or acetate. Slow-whole-cell patch-clamp
experiments showed no additional effect of CCH on the membrane voltage (V
m) measured after TriMA or acetate application. We conclude that pHi is a physiological modulator of hormonal effects in HT29 cells, as the [Ca2+]i responses to agonists were significantly changed at already slightly altered pHi. The measurements of InsP
3, cell volume and V
m show that pHi must act distally to the InsP
3 production, and not via changes of cell volume or V
m.
Received: 21 March 1997 / Received after revision: 14 May 1997 / Accepted: 15 May 1997 相似文献
95.
目的:探讨电针治疗心肌缺血的作用机制。方法:从80只健康SD大鼠中随机选择10只作为正常对照组,其余大鼠结扎冠状动脉旋前降支复制心肌缺血动物模型。选取模型复制成功的大鼠随机分为模型组、“神门”穴组、“内关”穴组和“太渊”穴组,每组10只。分别电针大鼠左侧“神门”穴、“内关”穴和“太渊”穴,每次刺激10min,每目1次,连续3d。采用酶联免疫吸附试验测定下丘脑室旁核区去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)、5-羟色胺(5-hydroxytryptamine,5-HT)含量。结果:模型组大鼠下丘脑室旁核区NE、DA和5-HT含量均显著下降(P〈0.01)。与模型组比较,“内关”组和“神门”组NE、DA、5-HT含量均显著升高(P〈0.01);“太渊”组仅NE含量显著升高(P〈0.05)。结论:电针“神门”、“内关”穴治疗心肌缺血的机制与其促进下丘脑室旁核区单胺类递质的释放有关。 相似文献
96.
目的研究脑梗死正常、病变区表观弥散系数差值对出血性转化风险的评估价值。方法选取我院2014年7月-2016年6月神经内科收治的50例早期脑梗死患者,入院后给予螺旋CT和MRI常规颅脑平扫,所有患者均行DWI、ADC扫描,在患者MR ADC图上分别测量并计算脑梗死正常区、病变区的ADC差值;发病2周后随访行MR复查,观察HT发生情况,并进一步分析HT和ADC差值的相关性。结果通过随访复查,50例CI患者中共有5例出现HT,未发生HT(NHT)为45例,HT发病率为10.0%,低于未发生HT(NHT)比重90.0%;早期ADC差值测量显示5例明显205.5×10-6mm2/s,且与随访复查出现HT的5例患者完全吻合,ADC差值预测体现较好的准确度和特异性;HT患者ADC差值(221.4±10.2)×10-6mm2/s高于NHT(145.3±11.4)×10-6mm2/s,差异显著(P0.05)。结论早期脑梗死正常、病变区ADC差值测量能较好的反映梗死灶出血状况,本次研究认为当ADC差值205.5×10-6mm2/s即提示HT发生的高风险可能,对临床预测评估HT和指导治疗具有较高的参考价值。 相似文献
97.
目的 :探讨高血压 ( HT)引起急性心肌梗死 ( AMI)的临床特点。方法 :分析 46例有 HT病史和 45例无高血压病史 ( NHT)的 A MI临床资料。结果 :HT组出现室性心律失常、心功能恶化、心肌再梗死、住院死亡率均高于 NHT,有显著差异 ( P<0 .0 5 )。结论 :高血压是影响 AMI预后的一个高危因素 ,严重心脏并发症较多 ,近期预后较差。 相似文献
98.
Tarek Antoun Ahmed Iraqi Loïg Kergoat Luciano Miozzo Abderrahim Yassar 《Macromolecular chemistry and physics.》2011,212(11):1129-1136
A simple and efficient approach for the preparation of rod‐coil block copolymers comprising oligo‐ and polythiophenes blocks together with PMMA or PS blocks is described. The block copolymers were prepared using a two‐step procedure. α,ω‐dicarboxy‐terminated oligothiophenes and carboxy terminated poly(3‐hexylthiophene) were first prepared. These were then reacted with P4S10 in a second step to generate the α,ω‐thioester terminated oligothiophenes and poly(3‐hexylthiophene)s which were subsequently used in a one‐pot reaction as RAFT polymerization agents with methylmethacrylate and styrene. The di‐ and tri‐block copolymers hence obtained were fully characterized, both in solution and as thin films.
99.
100.