全文获取类型
收费全文 | 480篇 |
免费 | 25篇 |
国内免费 | 13篇 |
专业分类
基础医学 | 12篇 |
临床医学 | 101篇 |
内科学 | 10篇 |
皮肤病学 | 2篇 |
神经病学 | 112篇 |
特种医学 | 1篇 |
外科学 | 15篇 |
综合类 | 57篇 |
预防医学 | 3篇 |
眼科学 | 1篇 |
药学 | 172篇 |
中国医学 | 29篇 |
肿瘤学 | 3篇 |
出版年
2022年 | 3篇 |
2021年 | 5篇 |
2020年 | 11篇 |
2019年 | 6篇 |
2018年 | 8篇 |
2017年 | 10篇 |
2016年 | 11篇 |
2015年 | 11篇 |
2014年 | 35篇 |
2013年 | 39篇 |
2012年 | 40篇 |
2011年 | 41篇 |
2010年 | 28篇 |
2009年 | 25篇 |
2008年 | 24篇 |
2007年 | 41篇 |
2006年 | 28篇 |
2005年 | 23篇 |
2004年 | 20篇 |
2003年 | 18篇 |
2002年 | 18篇 |
2001年 | 12篇 |
2000年 | 3篇 |
1999年 | 4篇 |
1998年 | 4篇 |
1997年 | 16篇 |
1996年 | 10篇 |
1995年 | 6篇 |
1994年 | 6篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 2篇 |
1989年 | 1篇 |
1988年 | 1篇 |
1985年 | 2篇 |
排序方式: 共有518条查询结果,搜索用时 15 毫秒
101.
帕罗西汀对应激抑郁模型大鼠脑区蛋白激酶PKA、PKC和CaMKII活力的影响 总被引:2,自引:0,他引:2
目的 探讨帕罗西汀对应激抑郁模型大鼠脑区蛋白激酶PKA、PKC和CaMKII活力的影响.方法 将成年雄性SD大鼠随机分为6组:对照组(Ⅰ)、抑郁模型组(Ⅱ)、抑郁模型 给药1次组(Ⅲ)、抑郁模型 给药1周组(Ⅳ)、抑郁模型 给药2周组(Ⅴ)和抑郁模型 给药4周组(Ⅵ).抑郁模型为强迫大鼠游泳4周.采用同位素法检测蛋白激酶PKA、PKC和CaMKII的活力.结果 (1)在海马,Ⅱ、Ⅲ、Ⅳ、及Ⅴ组大鼠PKA[分别为(3.92±0,23)×10-2,(3.68±0.092)×10-2,(3.56±0.1)×10-2,和(3.52±0.18)×10-2]和CaMKII[分别为(12.89±0.31)×10-2,(15.08±2.07)×10-2,(16.32±2.87)×10-2,和(17.00±1.52)×10-2]活力明显低于Ⅰ组[PKA(5.63±0.41)×10-2;CaMKII(48.91±1.86)×10-2]和Ⅵ组[PKA(4.92±0.36)×10-2;CaMKII(46.74±1.34)×10-2(P<0.01或P<0.05);Ⅱ组大鼠PKC的活力[(0.55±0.017)×10-2]明显低于对照组[(1.48±0.27)×10-2](P<0.01),各用药组大鼠海马PKC活力与对照组比较差异无统计学意义(P>0.05)(2)在前额叶皮质,Ⅱ、Ⅲ,Ⅳ组大鼠PKA活力[分别为(0.9±0.027)×10-2,(0.92±0.081)×10-2,(0.92±0.028)×10-2]与对照组[(0.99±0.072)×10-2]比较差异无统计学意义(P>0.05);而V[(1.14±0.045)×10-2和Ⅵ[(1.27±0.040)×10-2组的PKA活性则显著高于其它四组(P<0.01);Ⅱ和Ⅲ组的PKC活性[分别为(0.15±0.013)×10-2,(0.14±0.007)×10-2)]均显著高于对照组[(0.099±0.0007)×10-2]和其它用药组(P<0.01),Ⅳ组PKC活性[(0.1±0.0006)x10-2]与Ⅰ组比较差异无统计学意义(P>0.05),Ⅴ和Ⅵ组PKC活性[分别为(0.077±0.0005)×10-2,(0.03±0.00017)×10-2]显著低于Ⅰ组(P<0.01);模型组[(6.84±0.22)×10-2]和各用药组[分别为(6.68±0.23)×10-2,(6.89±0.15)×10-2,(6.55±0.14)×10-2,(6.53±0.13)×10-2]的CaMKII活性显著低于埘照组[(16.57±0.19)×10-2](P<0.01).结论 帕罗西汀长期用药逆转慢性应激所致大鼠海鸟PKA、PKC和CaMKII活力降低,而对前额叶皮质PKA、PKC和CaMKII活力改变的作用复杂. 相似文献
102.
Lee P Shu L Xu X Wang CY Lee MS Liu CY Hong JP Ruschel S Raskin J Colman SA Harrison GA 《Psychiatry and clinical neurosciences》2007,61(3):295-307
The aim of the present paper was to compare the efficacy and safety of duloxetine with paroxetine in the acute treatment of major depressive disorder (MDD). In a randomized, double-blind trial of 8 weeks active treatment, patients with non-psychotic MDD were randomized to duloxetine 60 mg (n = 238) or paroxetine 20 mg (n = 240) once daily. Efficacy was primarily measured on change in the 17-item Hamilton Rating Scale for Depression (HAMD(17)) using a non-inferiority test with a margin of 2.2. Secondary efficacy measures included the HAMD(17) subscales, Hamilton Rating Scale for Anxiety, Clinical Global Impressions-Severity, Patient Global Impressions-Improvement, Somatic Symptoms Inventory and Visual Analog Scales (VAS) for pain. Safety measures included treatment-emergent adverse events (TEAE), vital signs, weight, laboratory analyses and electrocardiograms. Non-inferiority of duloxetine to paroxetine was demonstrated because the upper bound of the confidence interval for mean difference in HAMD(17) change (0.71) was less than the non-inferiority margin. Secondary efficacy end-points did not differ significantly between treatments with the exception of VAS back pain, where the pooled mean was lower in the duloxetine group (17.1) compared with the paroxetine group (20.3, P = 0.048). No significant differences were observed in the number of early discontinuations and overall TEAE. However, significantly greater proportions of patients in the duloxetine group experienced nausea and palpitations. No clinically relevant changes in laboratory values, vital signs, weight or electrocardiograms were observed with either treatment. The present study verifies the utility of duloxetine as an efficacious and safe treatment for both emotional and physical symptoms of MDD in this predominantly Asian patient sample. 相似文献
103.
目的观察重复经颅磁刺激联合帕罗西汀治疗女性抑郁症伴功能性胃肠病的疗效及安全性,并分析其作用机制。方法选取女性抑郁症伴功能性胃肠病患者60例,随机分为对照组及颅磁组(n=30)。对照组患者口服帕罗西汀治疗,颅磁组在对照组的基础上重复经颅磁刺激治疗。比较两组治疗前及治疗1周、2周、4周后抑郁、胃肠道症状改善情况,于治疗4周后评估治疗效果及不良反应情况;比较两组治疗前、治疗4周后神经内分泌指标多巴胺、5-羟色胺(5-HT)、皮质醇 变化情况。结果治疗1周、2周、4周后,两组间汉密尔顿抑郁量表-17项(HAMD-17)、胃肠道症状评定量表(GSRS)评分差异有显著性(P<0.05),且颅磁组低于对照组;治疗4周后,颅磁组总有效率高于对照组(P<0.05);两组不良反应发生率比较,差异无显著性(P>0.05);治疗4周后,颅磁组血清多巴胺、5-HT高于对照组,皮质醇低于对照组(P<0.05)。结论在帕罗西汀治疗的基础上联合重复经颅磁刺激有利于改善女性抑郁症伴功能性胃肠病患者抑郁及胃肠道症状,提高治疗效果,其机制可能与重复经颅磁刺激改善神经内分泌指标相关;且该疗法具有较高的安全性。 相似文献
104.
Addition of an NK1 receptor antagonist to an SSRI did not enhance the antidepressant effects of SSRI monotherapy: results from a randomized clinical trial in patients with major depressive disorder 下载免费PDF全文
105.
晶体生长机制的研究是实现结晶过程控制尤其是以溶液为媒介的多晶型转换过程控制的关键。本研究利用经验模型研究了盐酸帕罗西汀的晶体生长机制。结果表明,随温度的升高,初级成核速率升高,而固液界面张力却存在微弱下降趋势;晶体生长机制为表面反应控制;晶体生长属于与粒度或体积无关的连续生长模式。 相似文献
106.
SPILIOS V. ARGYROPOULOS JANE A. HICKS JOHN R. NASH CAROLINE J. BELL ANNE S. RICH DAVID J. NUTT SUE WILSON 《Journal of sleep research》2009,18(3):342-348
It has been suggested that increase in delta sleep ratio (DSR), a marker for the relative distribution of slow wave activity (SWA) over night time, is associated with clinical response to antidepressant treatment. We examined this index and its relationship to rapid eye movement (REM) suppression before and during long-term treatment with nefazodone, which does not suppress REM sleep, and paroxetine which does. The effect of serotonin (5-HT2A ) receptor blockade on the evolution of SWA during treatment was also investigated. In a double-blind, randomised, parallel group, 8-week study in 29 depressed patients, sleep electroencephalograms were performed at home at baseline, on night 3 and 10, and at 8 weeks of treatment with either paroxetine or nefazodone. SWA was automatically analysed and a modified DSR (mDSR) was derived, being the ratio of amount of SWA in the first 90 min of sleep to that in the second plus third 90-min periods. At baseline, the pattern of SWA over night time was similar to other reports of depressed patients. mDSR improved over the course of treatment; there was no difference between remitters and non-remitters but there was a significant drug effect and a significant drug × time effect with paroxetine patients having a much higher mDSR after treatment, regardless of clinical status. SWA and REM during antidepressant treatment appear to be interdependent and neither of them alone is likely to predict response to treatment. Higher mDSR did not predict therapeutic response. 5-HT2A blockade by nefazodone does not increase SWA above normal levels. 相似文献
107.
108.
OBJECTIVES: This study evaluated the effectiveness and tolerability of paroxetine controlled release (CR) for the treatment of Korean patients with major depressive disorder (MDD) in a naturalistic treatment setting. METHODS: One hundred and ninety patients with MDD were enrolled in this study. The Hamilton Depression Rating Scale-17 item (HAMD-17) and Clinical Global Impression-Severity (CGI-S) scores were measured at the baseline (day 0) and at weeks 1, 2, 4, and 8 (endpoint). The primary measure of effectiveness was a change in the mean HAMD-17 scores from the baseline to the endpoint. The secondary effectiveness measures included a decrease in the HAMD-17 scores of 50% or more at the endpoint compared with the baseline and a change in the mean CGI-S scores from the baseline to the endpoint. Remission was defined as a HAMD-17 score < or = 7 at the endpoint. RESULTS: The HAMD-17 scores decreased by 56.5% (observed difference, OD = -13.3) (t = 26.63, p < 0.0001) from the baseline. The CGI-S scores also decreased by 50.0% (OD = -2.3) (t = 24.47, p < 0.0001). The response and remission rate at the endpoint was 64.2 and 48.4%, respectively. The adverse events were tolerable. No unexpected or serious side effects were observed. CONCLUSIONS: Despite the methodological limitations, this study demonstrated that paroxetine CR is effective and tolerable for treating patients with MDD in an East Asian population. 相似文献
109.
Miyamoto K Yoshimura R Ueda N Sugita A Umene W Hori H Mitoma M Nakamura J 《Human psychopharmacology》2007,22(7):483-490
In the present study, we examined the effects of acute treatment with paroxetine on the consumption of cigarette smoking and caffeine in 65 patients who met the DSM-IV criteria for major depressive disorder (M/F: 28/37, age: 48 +/- 15 years). Plasma levels of cotinine or caffeine were analysed using high-performance liquid chromatography (HPLC). The amount of cigarette smoking and plasma levels of cotinine, but not caffeine, decreased 4 weeks after paroxetine treatment. There was no difference between smokers and nonsmokers with respect to their response to paroxetine treatment. In addition, plasma 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in responders to paroxetine treatment was higher than those in nonresponders, and there was a negative correlation between the changes in plasma MHPG levels and the changes in Hamilton rating scale for depression (Ham-D) scores before and 4 weeks after paroxetine administration. These results suggest that paroxetine has the potential to reduce the amount of cigarette smoking in depressed smokers, and we reconfirmed our previous results that depressed patients with higher plasma MHPG levels had better response to paroxetine treatment than those with lower plasma MHPG levels using larger depressed samples. 相似文献
110.
Cole JA Ephross SA Cosmatos IS Walker AM 《Pharmacoepidemiology and drug safety》2007,16(10):1075-1085
PURPOSE: To refine a preliminary analysis identifying a possibly increased prevalence of malformations among infants born to women exposed to paroxetine in the first trimester. METHODS: This study used data from UnitedHealthcare, a large U.S. insurer, using datasets originally for a study of bupropion in pregnancy. We identified women with a live-born delivery between January 1995 and September 2004. We classified women according to their first trimester mono- or mono/polytherapy exposure to paroxetine and other antidepressants. We confirmed malformation cases by medical record abstraction. We calculated the adjusted odds ratios (AORs) through logistic regression. RESULTS: For paroxetine, there were 815 infants among 791 women exposed as monotherapy, and 1020 infants among 989 women exposed as mono- or polytherapy. For other antidepressants, there were 4198 infants among 4072 women exposed as monotherapy, and 4936 infants among 4767 women exposed as mono- or polytherapy. AORs for all congenital malformations associated with paroxetine were 1.89 (95%CI 1.20-2.98) for monotherapy, and 1.76 (95%CI 1.18-2.64) for mono- or polytherapy. AORs for cardiovascular malformations associated with paroxetine were 1.46 (95%CI 0.74-2.88) for monotherapy, and 1.68 (95%CI 0.95-2.97) for mono- or polytherapy. CONCLUSIONS: These more detailed paroxetine findings confirm previous findings of analyses of these data among women exposed to all types of antidepressants. The present findings are consistent with other recent results suggesting the possibility of a modestly increased occurrence of congenital malformations following first trimester exposure to paroxetine compared to other antidepressants. 相似文献