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1.
HELEN J. GILL JAMES L. MAGGS STEPHEN MADDEN MUNIR PIRMOHAMED & B. KEVIN PARK 《British journal of clinical pharmacology》1996,42(3):347-353
1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800 mg sulphamethoxazole and 160 mg trimethoprim) alone or 1 h after either fluconazole (150 mg) or ketoconazole (200 mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24 h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N4 -acetyl sulphamethoxazole, or sulphamethoxazole N1 -glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points. 相似文献
2 Ten healthy male volunteers were given co-trimoxazole (800 mg sulphamethoxazole and 160 mg trimethoprim) alone or 1 h after either fluconazole (150 mg) or ketoconazole (200 mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24 h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points. 相似文献
2.
The MIC values of the antifungal drug ketoconazole were evaluated on 66 Candida albicans strains. These strains were isolated from 26 HIV-1 infected patients with oral recurrent candidosis. Each episode of oral candidosis observed in these patients was orally treated with ketoconazole (200 mg/day) until the clinical disappearance of the lesions. The most frequent MIC values were 20 micrograms/ml and 10 micrograms/ml, observed in 37 and 19 isolates respectively. Only strains from five patients showed changes in their susceptibility to ketoconazole. This fact could indicate that a different strain causes the subsequent reappearance of the oral lesions, rather than the drug selecting resistant fungal strains. Our results stress the role of host characteristics in the occurrence of candidal infections, pointing to the progressing failure of the immunological response as the most important factor responsible for the recurrence of oral candidosis during HIV-1 infection. 相似文献
3.
胶束电动毛细管色谱法测定复方酮康唑霜中酮康唑和特美呋的含量 总被引:1,自引:0,他引:1
目的:毛细管电泳法测定酮康唑霜中酮康唑和特美味的含量。方法:分离缓冲液为胆汁酸钠(70 mmol/L)-三羟甲基氨基甲烷-磷酸(50 mmol/L)(pH 8.14),分离电压30 kV、温度25 C、50 μm(内径)×48.5cm(有效长度40cm)空心熔融石英毛细管柱、检测波长240nm。结果:以丙酸睾酮为内标,酮康唑质量浓度在140.5~702.5 μg/ml、特美呋质量浓度在151~755μg/ml之间成良好的线性关系;加样回收率分别为95.4%~103.9%、95.9%~102.6%,RSD%分别为2.8%~4.2%(n=3)、2.9%~3.6%。结论:本法简便、快速、可靠,可用于该复方制剂中酮康唑及特美呋的含量测定。 相似文献
4.
Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome. 总被引:1,自引:1,他引:0
Amr El-Husseini Fathy El-Basuony Ahmed Donia Ihab Mahmoud Nabil Hassan Nagy Sayed-Ahmad Mohamed Sobh 《Nephrology, dialysis, transplantation》2004,19(9):2266-2271
BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response. 相似文献
5.
Skin infection in a man immunosuppressed by corticosteroid treatment was found to be due to Pseudallescheria boydii. Although treatment is often unsatisfactory, infection in this patient responded well to oral ketoconazole and topical miconazole. 相似文献
6.
The effects of single oral doses of ketoconazole 400 mg and terbinafine 500 mg on the hepatic microsomal system have been investigated in 8 healthy male volunteers. Microsomal activity caffeine was assessed by following the metabolism of 3 mg/kg bodyweight i.v. administered 1 h after the drug. The inhibitory effect of terbinafine was more pronounced than that of ketoconazole: clearance was decreased from 1.34 ml.kg-1.min-1 in controls to 1.06 and 1.21 ml.kg-1.min-1, respectively, and the corresponding half-life was increased from 5.8 h in controls to 7.6 and 6.7 h, respectively. The apparent volume of distribution remained unchanged. The serum levels of the antimycotics were within the therapeutic range in each subject. Although all three substances are metabolised by microsomes, the kinetic parameters (Cmax, half-life, elimination constant) of the antimycotics were poorly if at all correlated with the elimination of caffeine. 相似文献
7.
De Coster R. Caers I. Haelterman C. Debroye M. 《European journal of clinical pharmacology》1985,29(4):489-493
Summary The effect of a single oral dose of 400 mg ketoconazole, given as an 80 mg/ml suspension, on total and physiologically free (i.e. non-sex hormonebound) testosterone and 17-oestradiol has been investigated in 6 healthy male volunteers. The two steroids fell to nadir levels of 18 and 60% of their respective initial concentrations 6 hours after drug intake, and then completely recovered. Although in vitro slight displacement of testosterone from the sex-hormone binding globulin, by high doses of ketoconazole was found, the physiologically free concentration of testosterone in vivo was closely correlated with that of the total hormone, suggesting that there is no direct interference with sex-hormone binding globulin in vivo. Plasma LH and FSH were not significantly modified by treatment. The effect of ketoconazole on plasma oestradiol levels was less pronounced and was not clearly related to a block of the aromatase system, as reported in vitro.This work was presented in part at the International Symposium on the Regulation of Androgen Actions, Montreal, 29th June–1st July 1984 相似文献
8.
G. S. Hughes S. F. Francom C. R. Spillers T. V. Ringer 《European journal of clinical pharmacology》1990,38(6):555-560
Summary In this randomized, open-label trial, 24 subjects were studied. There were 12 subjects with essential hypertension and 12 normotensive controls who received, after an initial control period, 48 h of treatment with a transdermal estradiol patch or ketoconazole tablets every 8 h for six doses, or in combination. LHRH (100 g) and ACTH (250 g) were given at 48 h of each treatment. Each treatment was one week apart.In both normotensive and hypertensive men ketoconazole reduced adrenal and gonadal androgens, raised 11-deoxycortisol and 17 -hydroxyprogesterone levels; blunted the rise of cortisol to ACTH and had no effect on the response of LH to LHRH. Transdermal estradiol raised serum estradiol levels, blunted the time to peak plasma concentration of LH to LHRH and produced a normal response to ACTH. Although baseline level of total and free testosterone and DHEA-S were lower in hypertensive men, the response of the pituitary (LH) to LHRH and adrenal axis with ACTH were similar in both normotensive and hypertensive men. Blood pressure was unaffacted by any of the treatment interventions in either normotensive or hypertensive men.Although ketoconazole or transdermal estradiol reduce androgens, there was no evidence that this reduction in androgens was involved with the short term regulation of blood pressure in hypertensive men. 相似文献
9.
口服伊曲康唑与外用酮康唑洗剂联合治疗糠秕孢子菌性毛囊炎 总被引:2,自引:2,他引:2
王晖 《中国新药与临床杂志》2005,24(8):647-648
目的:观察口服伊曲康唑与外用酮康唑洗剂联合治疗糠秕孢子菌性毛囊炎的疗效。方法:选择临床症状典型,经真菌学检查确诊的糠秕孢子菌性毛囊炎病人52例,分为2组。治疗组27例中男性18例,女性9例,年龄(28±s11)a,与餐同服或餐后即服伊曲康唑200mg,qd,连续7d,同时外用2%酮康唑洗剂,qd,连续用药4wk。对照组25例中男性19例,女性6例,年龄(29±10)a,单纯口服伊曲康唑200mg,qd,疗程同上。观察用药后1,4wk,2组疗效。结果:对照组1,4wk有效率分别为52%和68%,治疗组分别为59%和96%,2组1wk疗效差异无显著意义,4wk疗效治疗组优于对照组。结论:口服伊曲康唑与外用酮康唑洗剂治疗糠秕孢子菌性毛囊炎疗效好。 相似文献
10.
单、复凝聚法制备酮康唑微囊的性状和包封率比较 总被引:3,自引:0,他引:3
目的:比较单、复凝聚法制备微囊的外观性状和包封率,为进一步研究微囊的制备工艺打下基础。方法:以酮康唑作为囊芯物,用明胶和阿拉伯胶作囊材,采用常规的单、复凝聚法分别制备酮康唑微囊,并在光学显微镜下比较其外观性状;采用单波长紫外分光光度法建立微囊中酮康唑含量测定方法,在此基础上计算其药物包封率。结果:2种方法所得的微囊均为白色粉末,采用单凝聚法得到的微囊平均粒径为32.20μm, 相对包封率为56.11%;复凝聚法制备的微囊则分别为7.99μm和83.42%。结论:采用相分离-凝聚法制备微囊时,复凝聚法所得结果较好。 相似文献