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71.
头孢氨苄缓释片在健康人体内的生物利用度和药物动力学 总被引:2,自引:0,他引:2
目的:比较头孢氨苄缓释片和普通胶囊的生物利用度和药物动力学。方法:10例健康志愿者分别单剂量口服500mg头孢氨苄缓释片和普通胶囊,血药浓度测定方法为HPLC法。结果:两种剂型体内过程均符合一室开放模型,缓释片的达峰时间(Tmax)为(2.58±0.59)h,峰浓度(Cmax)为(10.08±1.68)μg/ml.吸收速率常数(Ka)为(0.90±0.53)/h,消除速率常数(Ke)为(0.26±0.02)/g,半衰期(T1/2)为(2.67±0.23)h,清除率(Cl)为(6.93±1.71)L/h,分布容积(Vd)为(26.66±6.72)L,药一时曲线下面积(AUC)为(48.31±9.32)μg·h/ml。两种剂型T一C一Ka、Ke、T1/2和Cl均存在显著性差异(P<0.01),Vd、AUC无显著性差异(P>0.05);缓释片的相对生物利用度为(104.90±8.35)%。结论:缓释片的吸收减慢,Tmax推迟,T1/2延长,可减少服药次数,提高药物治疗的顺应性。 相似文献
72.
甲氧基红霉素对卡马西平药物动力学的影响 总被引:2,自引:0,他引:2
应用荧光偏振免疫法,测定6只家兔po卡马西平及连续多次po用搓甲氧基红霉素后po卡马西平的血清卡马西平浓度,用3p87程序包按二室模型对数据进行处理并进行统计学分析。 相似文献
73.
吉西他滨联合5-氟尿嘧啶和四氢叶酸治疗晚期胰腺癌的临床研究 总被引:1,自引:0,他引:1
目的 评价 5 氟尿嘧啶和四氢叶酸联合化疗与加用吉西他滨后治疗晚期胰腺癌的疗效和不良反应 ;以及 5 氟尿嘧啶药物代谢动力学指标的改变。方法 43例晚期胰腺癌患者分为实验组 ( 2 2例 )和对照组 ( 2 1例 )。实验组 :吉西他滨 10 0 0mg/m2 ,第 1,8,16天静脉滴注 ,5 氟尿嘧啶 40 0mg/m2 和四氢叶酸 10 0mg/m2 于第 1~ 5天静脉滴注 ;对照组 :5 氟尿嘧啶 40 0mg/m2 和四氢叶酸 10 0mg/m2 在第 1~ 5天静脉滴注 ,均以每 4周为 1疗程 ,持续 4个疗程。结果 实验组完全缓解 (CR) 1例 ( 4 .5 %) ,部分缓解 (PR) 6例 ( 2 7.3 %) ,临床受益反应率 (CBR)为 68.2 %;对照组无CR ,PR3例 ( 14 .3 %) ,CBR有效率 3 3 .3 %。实验组出现不良反应的数量和严重程度较对照组提高且差异具有显著性。实验组 5 氟尿嘧啶血浆药物浓度、血浆峰值提高 ,血浆半衰期延长。结论 吉西他滨与 5 FU、四氢叶酸联合应用治疗晚期胰腺癌有一定的客观疗效 ,可明显改善患者的生存质量 ,但不良反应也随之提高。上述变化与吉西他滨改变 5 FU的药物代谢动力学有关 相似文献
74.
M. Depré D. J. Margolskee A. Van Hecken J. S. Y. Hsieh A. Buntinx P. J. De Schepper J. D. Rogers 《European journal of clinical pharmacology》1992,43(4):431-433
Summary The disposition of the enantiomers of MK-571 (MK-0679 and L-668,018) following single i. v. doses of MK-571 (L-660,711) was studied in a three way cross-over study in 12 healthy male volunteers. Each volunteer received 75 mg, 300 mg and 600 mg i. v. doses of MK-571 at weekly intervals.The disposition of both enantiomers appeared dose-dependent, since the AUC increased disproportionately faster than the dose. The dose dependency was much more pronounced for L-668,018: its AUC increased 6-fold from the 75 to the 300 mg dose, 16-fold from 75 to 600 mg and 2.7 fold from 300 to 600 mg. For MK-0679, the corresponding increases in AUC were 4.8-, ll-, and 2.3 fold. Regardless of dose, the elimination of L-668,018 was more rapid than that of MK-0679.The disposition of MK-0679 needs to be investigated independently to detect any potential influence of L-668,018 on its disposition. 相似文献
75.
G. Sutherland M. A. H. Russell J. Stapleton C. Feyerabend O. Ferno 《Psychopharmacology》1992,108(4):512-518
Plasma nicotine concentrations following administration by two types of nasal nicotine spray were compared in ten subjects. Absorption was particularly rapid during the first 2.5 min, the average rise in blood nicotine concentrations during this time being 8.6 ng/ml for the two products, followed by a small further rise to an average peak increase of 10.5 ng/ml 5 min after the dose of 2 mg nicotine base (mean 27.8 micrograms/kg). Despite a four-fold Cmax variation between subjects, the levels of individual subjects were fairly consistent across the two products. There were no significant differences between the two products in blood nicotine concentrations or cardiovascular responses, and the correlation between the AUCs from the two products was 0.68 (P = 0.01). Eight subjects reported subjective feelings of light-headedness or slight dizziness, which are not typical after slower absorption from nicotine gum or skin patches. Blood nicotine levels within the smoking range were soon built up with repeated doses, even in the subject with the least efficient nasal absorption. In a second study of ad libitum use under clinical conditions both products appeared sufficiently acceptable for therapeutic use as an aid to smoking cessation. There was no tendency to escalate to excessive use over 4 weeks, and blood nicotine concentrations in nine subjects averaged only 44% of their prior smoking levels. Only one subject had levels equivalent to prior smoking and possible reasons why this was not more common are discussed. 相似文献
76.
77.
G. Vinçon C. Baldit P. Couzigou F. Demotes-Mainard L. Elouaer-Blanca Dr. B. Bannwarth B. Begaud 《European journal of clinical pharmacology》1992,43(5):559-562
Summary The pharmacokinetics of famotidine has been investigated in ascitic cirrhotic patients. 10 decompensated cirrhotic patients were studied (9 m, 1 f), who had normal renal function, and six healthy control subjects (4 m, 2 f), matched for age, sex and weight. Each subject received on two occasions, at least four days apart, a single oral (40 mg) or intravenous dose (20 mg) of famotidine, at 21.00 h in a randomised manner. Serial blood samples were collected and famotidine in plasma was determined by a HPLC/UV method. Plasma data were subjected to non compartmental pharmacokinetic analysis.There were no statistically significant differences in pharmacokinetic parameters between the two groups after either the intravenous or oral administration of famotidine.The findings suggest that the dose of famotidine may not require any adjustment in ascitic patients without renal failure. 相似文献
78.
Summary The pharmacokinetics of isradipine, a calcium-channel blocker, have been studied in eight patients on chronic haemodialysis. A single oral dose of 5 mg was administered on both a non-haemodialysis and a haemodialysis day and the plasma concentrations of isradipine were analyzed.The mean cmax, tmax, AUC, and t1/2 in plasma on the non-haemodialysis day were 5.2 ng·ml–1, 1.4 h, 23.8 ng·h·ml–1, and 3.1 h, respectively. The dialysis clearance of isradipine was negligible (5.0 ml·min–1).The t1/2 values during haemodialysis were not significantly different from those observed during the same period post dose on the non-haemodialysis day. The study demonstrates that supplemental doses of isradipine are not necessary in these patients since isradipine is not significantly removed by haemodialysis. 相似文献
79.
P. H. Mogensen L. Jórgensen J. Boas M. Dam A. Vesterager G. Flesch P. K. Jensen 《Acta neurologica Scandinavica》1992,85(1):14-17
The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required. 相似文献
80.
Luis H. Ramirez Morbize Juliéron Marc Bonnay Serge Koscielny Zhongxin Zhao Alain Gouyette Jean-Nicolas Munck 《Investigational new drugs》1995,13(1):51-53
Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed
that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs.
Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits,
and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment
course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis
andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory
effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further
trials in patients with squamous cell carcinomas. 相似文献