全文获取类型
收费全文 | 420篇 |
免费 | 20篇 |
国内免费 | 11篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 1篇 |
妇产科学 | 5篇 |
基础医学 | 68篇 |
口腔科学 | 9篇 |
临床医学 | 52篇 |
内科学 | 106篇 |
神经病学 | 26篇 |
特种医学 | 4篇 |
外科学 | 19篇 |
综合类 | 25篇 |
预防医学 | 3篇 |
眼科学 | 4篇 |
药学 | 115篇 |
中国医学 | 12篇 |
出版年
2022年 | 2篇 |
2021年 | 3篇 |
2020年 | 7篇 |
2019年 | 5篇 |
2018年 | 5篇 |
2017年 | 9篇 |
2016年 | 10篇 |
2015年 | 7篇 |
2014年 | 9篇 |
2013年 | 28篇 |
2012年 | 10篇 |
2011年 | 12篇 |
2010年 | 21篇 |
2009年 | 28篇 |
2008年 | 22篇 |
2007年 | 8篇 |
2006年 | 16篇 |
2005年 | 14篇 |
2004年 | 25篇 |
2003年 | 14篇 |
2002年 | 11篇 |
2001年 | 10篇 |
2000年 | 11篇 |
1999年 | 11篇 |
1998年 | 11篇 |
1997年 | 22篇 |
1996年 | 15篇 |
1995年 | 9篇 |
1994年 | 8篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 4篇 |
1987年 | 5篇 |
1986年 | 9篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 3篇 |
1979年 | 2篇 |
1978年 | 2篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1972年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有451条查询结果,搜索用时 562 毫秒
11.
《Expert opinion on pharmacotherapy》2013,14(5):845-856
Nicorandil is an anti-anginal agent that has been used in the United Kingdom for over 6 years and is becoming increasingly popular. It induces coronary and peripheral vasodilatation via a dualistic mode of action, mediated by the opening of potassium-ATP channels (KATP) and its nitrate effect by stimulation of adenyl cyclase, with an increase in cGMP levels. Comparison to nitrates and other anti-anginal agents have shown it to be of equal efficacy in relieving ischaemic symptoms. Recent evidence suggests a role for nicorandil as a myocardial preconditioning agent but this may be limited by systemic vasodilatation. There is ongoing research into its role in improving the long-term outcome of patients with ischaemic heart disease (IHD). It has been shown to be of proven efficacy in the treatment of IHD and further research will clarify other uses of this agent. 相似文献
12.
13.
Chi-Chung Li Steve Vermeersch William S Denney William P Kennedy John Palcza Adrianna Gipson Tae H Han Rebecca Blanchard Inge De Lepeleire Marleen Depré M Gail Murphy Kristien Van Dyck Jan N de Hoon 《British journal of clinical pharmacology》2015,79(5):831-837
Aims
Calcitonin gene related peptide (CGRP) receptor antagonists are effective acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model has been developed to provide target-engagement information in healthy volunteers. In the model, CGRP release is provoked after dermal capsaicin application, by activating transient receptor potential vanilloid-type-1 (TRPV1) receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to assess the predictability of the CIDV response to migraine clinical efficacy.Methods
An integrated population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the exposure−response relationship for CIDV inhibition by CGRP and TRPV1 receptor antagonists. MK-3207 dose−response predictions were made based on estimated potency from the PK/PD model and mean plasma concentrations observed at the doses investigated.Results
The results suggested that a 20 mg dose of MK-3207 (EC50 of 1.59 nm) would be required to attain the peripheral CIDV response at a target level that was shown previously to correlate with 2 h clinical efficacy based on phase 3 telcagepant clinical data, and that a plateau of the dose−response would be reached around 40–100 mg. These predictions provided a quantitative rationale for dose selection in a phase 2 clinical trial of MK-3207 and helped with interpretation of the efficacy results from the trial.Conclusions
The integrated CIDV PK/PD model provides a useful platform for characterization of PK/PD relationships and predictions of dose−response relationships to aid in future development of CGRP and TRPV1 receptor antagonists. 相似文献14.
Aims/hypothesis Insulin has nitric-oxide-dependent vasodilatory effects in muscle, including capillary recruitment, that enhance access for itself and glucose. However, nitric-oxide-dependent vasodilators other than methacholine do not enhance insulin action. Our hypothesis is that methacholine, unlike bradykinin, enhances insulin-mediated glucose uptake in muscle by augmenting capillary recruitment.Methods Local infusion of either methacholine or bradykinin into one leg of the anaesthetised rat was made during physiological insulin (3 mU·kg–1·min–1) infusion under euglycaemic conditions and without affecting systemic blood pressure. Whole-body glucose infusion was determined, as was femoral blood flow, 2-deoxyglucose uptake into calf muscles and the metabolism of infused 1-methylxanthine, a measure of capillary recruitment for each leg.Results Methacholine alone (0.3 µmol·l–1) increased femoral arterial blood flow, increased capillary recruitment but had no effect on 2-deoxyglucose uptake of the test leg relative to the contra-lateral control leg. Insulin alone (systemically) required a glucose infusion rate of 8.7 mg·kg–1·min–1 to maintain euglycaemia, increased 2-deoxyglucose uptake and capillary recruitment, but was without effect on femoral blood flow in either leg. Local methacholine with systemic insulin infusion increased femoral blood flow, 2-deoxyglucose uptake and capillary recruitment in the test leg only. Bradykinin (0.07 µmol·l–1), alone or with insulin, administered in a manner that increased femoral blood flow similarly to methacholine, did not affect 2-deoxyglucose uptake or capillary recruitment.Conclusions/interpretation Methacholine but not bradykinin enhances insulin-mediated muscle glucose uptake in vivo. We conclude that methacholine acts at specific sites in the vasculature of muscle to stimulate capillary recruitment and thereby enhance insulin access. 相似文献
15.
Guang‐Yuan Mar Ming‐Ting Chou Hsien‐Hui Chung Nien‐Hua Chiu Mei‐Fen Chen Juei‐Tang Cheng 《International journal of experimental pathology》2013,94(1):17-24
The role of imidazoline receptors in the regulation of vascular function remains unclear. In this study, we evaluated the effect of agmatine, an imidazoline receptor agonist, on systolic blood pressure (SBP) in spontaneously hypertensive rats (SHRs) and investigated the expressions of imidazoline receptors by Western blot. The isometric tension of aortic rings isolated from male SHRs was also estimated. Agmatine decreased SBP in a dose‐dependent manner in SHRs but not in the normal group [Wistar–Kyoto (WKY) rats]. This reduction in SBP in SHRs was abolished by BU224, a selective antagonist of imidazoline I2‐receptors. Higher expression of imidazoline receptors in SHR was observed. Moreover, agmatine‐induced relaxation in isolated aortic rings precontracted with phenylephrine or KCl. This relaxation was also abolished by BU224 but was not modified by efaroxan, an imidazoline I1‐receptor antagonist. Agmatine‐induced relaxation was also attenuated by PNU 37883, a selective blocker of vascular ATP‐sensitive potassium (KATP) channels. Additionally, vasodilatation by agmatine was reduced by an inhibitor of protein kinase A (PKA). We suggest that agmatine can lower blood pressure in SHRs through activation of the peripheral imidazoline I2‐receptor, which is expressed more highly in SHRs. 相似文献
16.
目的通过建立离体小动脉血管内皮去除的研究方法,提高微血管测量技术研究数据的可信度。方法选取♂自发性高血压大鼠(SHR)和正常血压大鼠(WKY),测量血压后,获取肠系膜动脉环。采取机械(血管环围绕电极尖端旋转、推注气体)和药物(L-NAME和吲哚美辛)相结合的方式去除内皮。采用压力肌动图技术检测苯肾上腺素(PE)、乙酰胆碱(ACh)、硝普钠(SNP)对肠系膜动脉直径变化的影响。结果(1)SHR血压值高于WKY大鼠(P<0.01);(2)PE浓度依赖地收缩肠系膜动脉。内皮完整和内皮去除时,与WKY相比,SHR的收缩增强(P<0.05);(3)ACh、SNP能够浓度依赖地舒张肠系膜动脉。内皮完整时,与WKY相比,SHR的舒张减弱(P<0.01);内皮去除时,与WKY相比,SHR的舒张增强(P<0.01)。结论(1)成功建立离体微小动脉血管内皮去除的研究方法。(2)高血压大鼠存在明显的血管舒缩功能障碍。 相似文献
17.
18.
Breno José Acauan Filho Bartira Ercilia Pinheiro da Costa Patrícia Barcelos Ogando Matias Costa Vieira Ivan Carlos Antonello Carlos Eduardo Poli-de-Figueiredo 《Hypertension in pregnancy》2016,35(2):226-233
Objectives: To compare nitric oxide (NO) serum levels in women with and without preeclampsia. Methods: 106 women were classified into preeclampsia group (n = 40) and normotensive group (n = 66). NO content was measured in the serum. Clinical and laboratorial data were recorded for comparison. Results: Preeclampsia presented a significant increase in nitrate and NOx levels compared to the control group. Uric acid, gestational age, systolic and diastolic blood pressure, and creatinine showed correlation with nitrates and NOx. Conclusion: Increase of NO was observed in preeclampsia women. Failure in the mechanism of action, dependent on cyclic GMP, may justify this finding. 相似文献
19.
川芎嗪对急性心肌梗死溶栓后血管内皮功能的影响 总被引:11,自引:1,他引:11
目的:观察川芎嗪对急性心肌梗死(AMI)溶栓治疗后血管内皮功能的影响.方法:83例AMI患者按随机数字表法分为治疗组和对照组.治疗组43例,用尿激酶(UK)(10~15)×105 U加质量分数为0.9%的氯化钠100 ml静脉滴注,30 min滴完;阿司匹林0.3 g口服,每日1次,连服3 d,然后0.1 g,每日1次,长期服用.在用UK前10~30 min从另一静脉通路用川芎嗪240 mg加质量分数为0.9%的氯化钠400 ml静脉滴注,1.5~2.0 h滴完,其后按上述剂量每日1次,连用14 d.对照组40例,除不用川芎嗪外,其他均与治疗组相同.按无创冠状动脉再通标准判断溶栓再通率,治疗前后采静脉血,用酶法测定甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)浓度,并采用高分辨率血管外超声来检测两种治疗方法对患者肱动脉血流介导的内皮依赖性血管舒张功能(FMD)的影响.结果:两组溶栓再通率无差异[治疗组65.12%(28/43例),对照组65.00%(26/40例),P>0.05];两组治疗前后血脂亦无明显变化(P均>0.05);治疗组治疗2周后FMD为(6.53±0.41)%,较治疗前(2.46±0.21)%有显著改变(P<0.05).结论:川芎嗪对血管再通和血脂代谢均无影响,但能明显改善AMI患者的血管FMD. 相似文献
20.
Nancy T. Ross-Ascuitto Robert J. Ascuitto David Ramage Kathleen H. McDonough 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》1991,5(6):1011-1019
Summary Milrinone, a selective inhibitor of phosphodiesterase (PDE), was examined in neonatal hearts and in ventricular myocytes. Isolated, paced (180 beats/min), isovolumically beating hearts from pigs, <3 days of age, were perfused with an erythrocyte-enriched solution. In one group (control, n=6), milrinone was studied at perfusate concentrations of 1, 10, and 100 g/ml. In a second group (postischemia, n=10), hearts were subjected to 30 minutes of no-flow ischemic arrest, prior to the addition of milrinone. Left ventricular peak systolic pressure (PSP) and end-diastolic pressure, coronary flow (CF), heart rate (HR), and myocardial oxygen consumption (MVO2) were measured. The PSP averaged 100 mmHg during the baseline periods for both groups and decreased to 85 mmHg in those hearts subjected to ischemic arrest. In both groups, PSP increased 14% at the 1g/ml concentration of milrinone. No additional increases in PSP were observed in the control group at the higher concentrations. However, PSP increased 28% and 41% (p<0.05), in the postischemia group at the 10 and 100 g/ml concentrations, respectively. The CF averaged 3 ml/min/g during the baseline periods of both groups and increased significantly at each milrinone concentration. The HR in both groups increased to 200 and 250 beats/min at the 10 and 100 g/ml concentrations, respectively. Additionally, milrinone's effects in intact hearts were found to be comparable to those of isobutylmethyl xanthine (IBMX), a nonspecific PDE inhibitor. In isolated myocytes, however, milrinone produced only modest increases in cAMP levels, compared to IBMX. We conclude that milrinone has positive inotropic, coronary vasodilatory, and chronotropic effects in the neonatal pig heart. In particular, milrinone also was capable of reversing the contractile dysfunction that resulted when these immature hearts were subjected to 30 minutes of normothermic, no-flow ischemic arrest. Thus, milrinone may be a useful agent in the treatment of neonates with contractile dysfunction.Grant support has been supplied by The Louisiana Board of Regents, Louisiana Education Quality Support Fund, 150 Riverside Mall, Suite 129, Baton Rouge, LA 70801-1303. 相似文献