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1.
Erythromycin administration has been associated with a prolongation of cardiac repolarization in certain clinical settings.
This could be due to blockade of voltage-dependent K+ channels in the human heart. For this reason we examined the effects of erythromycin on a rapidly activating delayed rectifier
K+ channel (Kv1.5) cloned from human heart and stably expressed in human embryonic kidney cells. When examined using the whole-cell
patch clamp technique, erythromycin (100 μM) blocked Kv1.5 current in a time-dependent manner but required prolonged exposure
to do so. However, when we examined Kv1.5 current using inside-out macropatches, erythromycin applied to the cytoplasmic surface
rapidly (within 1-2 min) inhibited Kv1.5 current with an IC50 value of 2.6 x 10-5M (1.7 - 3.9 x 10-5M, 95% C.L.). The main effect of erythromycin was to accelerate the rate of Kv1.5 current decay thereby reducing the current
at the end of a prolonged voltage-clamp pulse. Erythromycin also blocked Kv1.5 current in both a voltage- and frequency-dependent
manner but had little effect on the activation kinetics, deactivation kinetics, or the steady-state inactivation properties
of Kv1.5. These data suggest that erythromycin acts as a blocker of an activated state of the Kv1.5 channel and that it may
access its binding site from the intracellular face of the channel. This study is the first to examine the effects of erythromycin
on a cloned human cardiac K+ channel. It is concluded that erythromycin blocks Kv1.5 at clinically relevant concentrations. Blockade of voltage-dependent
K+ channels in the heart could contribute to the alterations in cardiac repolarization that have been observed with erythromycin.
Received: 22 November 1996 / Accepted: 26 February 1997 相似文献
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功能性消化不良患者胃排空障碍与胃肠激素的关系 总被引:14,自引:0,他引:14
目的 探讨功能性消化不良(FD)患者胃排空障碍与胃肠激素间的关系。方法 对54例四患者进行胃排空检查,根据结果将其分为胃排空延缓的FD组(FDD组)和胃排空正常的四组(FDN组),另以17名正常人作为对照组。用放免法测定受试者血浆(空脂和餐后)、胃窦十二指肠粘膜组织的神经降压素(NT)和胃动宗(MTL)含量。结果 FDD组空脂和餐后血浆、胃窦和十二指肠粘膜组织的NT含量均明显高于对照组及FDN组。各组试餐前后血浆NT增幅差异无显著性。FDD组空脂和餐后血浆、胃窦和十二指肠粘膜组织的MIL含量均明显低于对照组及FDN组。各组十二指肠粘膜组织MTL含量均明显高于胃窦粘膜。结论 FD患者胃排空障碍与NT、MIL密切相关。NT、MIL在FD的发病机制中可能具有一定作用。 相似文献
4.
红霉素硬化疗法在非感染性疾病中的应用现状 总被引:3,自引:0,他引:3
红霉素的化学刺激作用一直被视为药物不良反应 ,近年通过对这一副作用进行深入的实验研究和临床验证 ,成功地用于许多难治性疾病的硬化治疗 ,取得了较好的效果。现就红霉素的硬化治疗新用途的国内外现状加以介绍。 相似文献
5.
目的 观察针刺加中药治疗功能性消化不良的临床疗效。方法 1 80例功能性消化不良患者随机分为 2组。治疗组 1 2 0例采用针刺加中药治疗 ,对照组 6 0例单用西药对症治疗 ,2组均治疗 2周后观察疗效。结果 治疗组总有效率为 95 .8% ,对照组为 83.4 % ,2组比较有显著性差异 (P <0 .0 1 )。结论 针刺加中药治疗功能性消化不良具有显著疗效 相似文献
6.
目的:研究小剂量红霉素联合孟鲁司特钠治疗儿童哮喘的临床疗效。方法:选取河南科技大学第一附属医院2020年1月至2022年6月诊治的90例哮喘患儿,采用随机对照方法分为观察组和对照组,各45例。对照组采用孟鲁司特钠治疗,观察组采用小剂量红霉素联合孟鲁司特钠治疗,比较两组患儿疗效、并发症、肺功能、儿童哮喘控制测试(C–ACT)评分、血清炎症因子及T淋巴细胞的差异。结果:观察组患儿治疗总有效率高于对照组,差异具有统计学意义(P <0.05);观察组患儿消化道症状、肝肾功能损伤、嗜睡及心率失常发生率高于对照组,但差异无统计学意义(P> 0.05);观察组患儿治疗后用力肺活量(FVC)、第1秒用力呼气量(FEV1)、呼气流量峰值(PEF)及C–ACT评分均高于对照组,差异具有统计学意义(P <0.05);观察组患儿治疗后血清白三烯D4(LTD4)及肿瘤坏死因子–α(TNF–α)、CD3+、CD4+及CD8+均低于对照组,差异具有统计学意义(P <0.05)。结论:小剂量红霉素联合孟鲁司特钠可改善哮喘患儿肺功... 相似文献
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8.
J. Lehtola P. Jauhonen A. Kesäniemi R. Wikberg A. Gordin 《European journal of clinical pharmacology》1990,39(6):555-558
Summary Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora. In order to evaluate the effect of erythromycin on gastrointestinal motility, 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA, 2-acetyl erythromycin stearate) 800 mg in a double-blind trial. The orocaecal transit time was measured using the hydrogen breath test with lactulose as the substrate. The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the front and t2 the bulk of lactulose reaching the colon.t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p < 0.05, ES vs placebo). t2 was 74 min, 64 min, and 46 min, respectively (p < 0.05, ES vs placebo). The difference between EA and ES was also significant. Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication.It was concluded that erythromycin shortens the orocaecal transit time in man and that EA affects the transit time slightly less than ES. 相似文献
9.
功能性消化不良患者胃膨胀感知的改变 总被引:3,自引:0,他引:3
目的研究功能性消化不良(FD)患者胃膨胀感知的改变。方法应用灌注导管测压仪研究了7例FD患者、5例FD并心理异常患者及5例正常人胃对容量刺激的感觉。结果发现FD患者胃对容量刺激的最低敏感性阈值、不适阈值及疼痛阈值分别为(195.7±65.3),(304.3±58.6),(464.3±47.2)ml,FD并心理异常患者为(123.0±40.3),(254.0±49.8),(466.0±76.4)ml,均明显低于正常人的(327.0±44.7),(532.4 ±107.4),(678.0±117.4)ml(P<0.01);三者的胃顺应性无明显改变。结论胃对容量刺激的感知过度敏感是FD发病的机制之一。 相似文献
10.
T. L. Peeters G. Matthijs G. Vantrappen 《Naunyn-Schmiedeberg's archives of pharmacology》1991,343(2):202-208
Summary Recent studies suggested that certain erythromycin A (EM-A) derivatives are motilin receptor agonists. As proposed by Itoh they may be called motilides. We have investigated the Ca2+-dependence of contractions induced by two potent motilides, ME-34 [de(N-methyl) 8,9-anhydroeryhtromycin A 6,9-hemiacetal] and EM-523 [de(N-methyl)-N-ethyl-8,9-anhydro-erythromycin A 6,9-hemiacetal], in duodenal tissues and compared the results with those previously obtained with motilin.Isometric and isotonic contractile responses of isolated longitudinal muscle sheets from the rabbit duodenum were tested under normal, Ca2+-free and depolarizing conditions. Prior to stimulation with motilides, the maximal response to acetylcholine was recorded and all responses were always expressed as a percentage of this response. Both motilides induced contractions in normally polarized tissue, with an EC50 of 26 ± 5 nM for ME-34 (n = 7), and 27 ± 5 nM for EM-5231 (n = 16) and maximal responses of respectively 88 ± 4% and 80 ± 3%. Like motilin, both compounds induced an extra-contraction in depolarized tissues. The EM-523 response in 140 mM K+under isotonic conditions was 84 ± 3% (n = 5) at 10–5
M, with an EC50 that was shifted to 65 ± 18 nM. Similar figures were obtained for ME-34. When Ca2+ was added to Ca2+-depleted strips, half-maximal Ca2+ values (in mM) were 1.10 ± 0.11 (n = 9) for EM-523 and 1.13 ± 0.12 (n = 3) for ME-34, as compared with 1.12 ± 0.13 (n = 7) for motilin and 2.8 ± 1.1 (n = 9) for K+. Both ME-34 and EM-523 also induced a transient contraction in Ca+-free solutions under isometric conditions. The response to EM-523 (5 × 10–6
M) was 49 ± 15% (n = 4) after 3 min. A maximal EM-523 -stimulation reduced a subsequent ACh response by 78 ± 7%, whereas EM-523 and ME-34 could not induce a contraction after ACh.We conclude that motilides depend upon external Ca2+ to a similar extent to motilin. Like motilin, they are also able to mobilize intracellular Ca Z + stores. Our results support the hypothesis that motilides act on motilin receptors.
Send offprint requests to T. L. Peeters at the above address 相似文献