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1.
Slices from rat midbrain containing the raphe nuclei and from hippocampus were prepared, loaded with [3H]5-HT and superfused and the resting and the electrically stimulated [3H]5-HT release was measured. The 5-HT3 receptor agonist 2-methyl-5-HT (1 to 10 μmol/l) increased the resting tritium outflow in superfused raphe nuclei slices, EC50 5.3 μmol/l. The 2-methyl-5-HT-induced increase of tritium outflow was an external Ca2+-independent process and was not altered by reserpine pretreatment but it was reversed by addition of the 5-HT uptake inhibitor fluoxetine (1 μmol/l). The 5-HT3 receptor antagonists ondansetron and GYKI-46 903 (1 μmol/l) did not antagonize the stimulatory effect of 2-methyl-5-HT on resting tritium outflow. 2-Methyl-5-HT in lower concentration increased the electrically induced tritium overflow from raphe nuclei slices (EC50 0.56 μmol/l) and also from hippocampal slices preloaded with [3H]5-HT. These effects were reversed by 1 μmol/l of ondansetron and GYKI-46903. The 5-HT3 receptor antagonists (1 μmol/l) were without effects on depolarization-evoked [3H]5-HT release at 2 Hz stimulation, when 10 Hz stimulation was used, ondansetron and GYKI-46 903 reduced the tritium overflow from raphe nuclei slices. These data indicate that 5-HT3 receptors positively alter depolarization-induced somatodendritic 5-HT release in the raphe nuclei. They also show that 2-methyl-5-HT is able to evoke 5-HT release not only from vesicles but also from cytoplasmic stores via a transporter-dependent exchange process. 相似文献
2.
A double-blind, placebo controlled trial was undertaken to examine the effect of the 5-HT3 antagonist, ondansetron .25 mg bd on cigarette withdrawal symptoms and on proportion of individuals maintaining continuous abstinence for 4 weeks in a smoking treatment programme. A total of 111 smokers were allocated to active or placebo conditions and began taking their study medication 2 weeks before the quit date. They attended the smokers clinic for weekly group treatment sessions. The results showed no evidence for less severe withdrawal symptoms or improved abstinence rates in the active medication group. They suggest that inhibiting 5-HT3 activity is not an effective method of controlling nicotine withdrawal or helping smokers to stop. 相似文献
3.
制备盐酸恩丹西酮缓释片并对影响释药的因素进行考察。以羟丙甲纤维素(HPMC)为骨架材料制备了盐酸恩丹西酮缓释片,通过正交设计试验优选最佳处方和工艺。对影响释药的因素,如HPMC的黏度和用量、填充剂的种类、制片工艺、润湿剂及释放介质pH等进行了考察。盐酸恩丹西酮缓释片体外释药符合Higuchi方程,HPMC的黏度、填充剂的种类及测定释放度的转速对该缓释片的释药几乎无影响,而制片工艺、润湿剂及释放介质pH值对缓释片释药影响较大。盐酸恩丹西酮缓释片在体外12h缓释效果较好。 相似文献
4.
目的:评价三种药物防治胃肠肿瘤化疗所致呕吐的价值。方法:90名患者随机分成三组,灭吐灵组(A组),吗丁啉组(B组),枢丹组(C组)。应用5-Fu+LV方案化疗5天,观察5天内三种药物的止吐效果。结果:A和B、C组比较有显著性差异(P〈0.05),B和C比较无显著性差异(P〉0.05)。结论:B组副作用少,疗效高,建议临床推广使用吗丁啉。 相似文献
5.
目的 验证国产盐酸格拉司琼注射预防恶性肿瘤患者化疗所致恶心与呕吐的有效性和安全性。方法 对69例接受以顺铂为主化疗和40例接受以蒽环类抗肿瘤药为主化疗的恶性肿瘤患者,采用前瞻性多中心随机对照试验,比较国产格拉司琼和国产上市恩丹西酮预防化疗所致恶心与呕吐的疗效和不良反应。结果 格拉司琼和恩丹西酮对预防强致吐和中度致叶化疗药物所致的急性和迟发性恶心与呕吐的疗效基本相同;不良反应变基本相似,以便秘、疲倦 相似文献
6.
7.
Colleen J. Gilbert William P. Petros James Vredenburgh Atif Hussein Maureen Ross Peter Rubin Randy Fehdrau Colleen Cavanaugh Donald Berry Craig McKinstry William P. Peters 《Cancer chemotherapy and pharmacology》1998,42(6):497-503
Purpose: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this
study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy.
Methods: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively
in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts
III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h.
A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic
monitoring of each drug used in the high-dose chemotherapy regimen was conducted. Results: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml · min) were lower than those of the control
patients (88.3 mg/ml · min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was
demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency
of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron
alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only.
Conclusion: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron
did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine.
Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide
metabolites so that clinical implications can be addressed.
Received: 28 October 1997 / Accepted: 9 March 1998 相似文献
8.
9.
Background
The potential for ondansetron to cause QT prolongation and fatal dysrhythmia is well-reported, including a 2011 FDA report on the topic. Few clinical trials evaluating this phenomenon in the ED setting exist, and only one is pediatric.Objective
We have sought to determine the effect of a standardized dose of intravenous ondansetron on the QTc duration of children under 14 years of age treated for gastroenteritis-associated vomiting in a pediatric ED. This study is modeled closely after an FDA “thorough QT study”.Methods
EGCs were obtained before and 15, 30, 45, and 60 min after a 0.15 mg/kg IV dose of ondansetron given for gastroenteritis-associated vomiting. QT intervals were measured manually with digital calipers, and the QTc interval calculated both by Bazett's (QTcB) and Fridericia's (QTcF) correction. A paired t-test comparing QTc was conducted, and frequency of categorical outcomes of prolongation > 30 msec, > 60 msec, and absolute prolongation > 450 msec, > 480 msec, and > 500 msec were evaluated.Results
In a 4-month period, 134 patients were included in the study, 46% were male. The average QTc prior to ondansetron administration was: QTcB 415 msec (95% CI 343–565) and QTcF 373 (95% CI 304–499). The mean difference in QTc after ondansetron was 0.4 msec for QTcB (95% CI ? 35–45 msec) and 0.1 msec for QTcF (95% CI ? 40–18 msec).Conclusion
In these children, 0.15 mg/kg of intravenous ondansetron did not cause prolongation of QTcB or QTcF measured 15 min after administration, nor at later times. 相似文献10.