全文获取类型
收费全文 | 1080篇 |
免费 | 60篇 |
国内免费 | 28篇 |
专业分类
儿科学 | 4篇 |
妇产科学 | 1篇 |
基础医学 | 27篇 |
临床医学 | 22篇 |
内科学 | 29篇 |
皮肤病学 | 2篇 |
神经病学 | 23篇 |
特种医学 | 15篇 |
外科学 | 18篇 |
综合类 | 85篇 |
预防医学 | 76篇 |
药学 | 812篇 |
中国医学 | 33篇 |
肿瘤学 | 21篇 |
出版年
2023年 | 10篇 |
2022年 | 9篇 |
2021年 | 27篇 |
2020年 | 16篇 |
2019年 | 15篇 |
2018年 | 13篇 |
2017年 | 18篇 |
2016年 | 31篇 |
2015年 | 24篇 |
2014年 | 30篇 |
2013年 | 97篇 |
2012年 | 35篇 |
2011年 | 49篇 |
2010年 | 28篇 |
2009年 | 63篇 |
2008年 | 58篇 |
2007年 | 63篇 |
2006年 | 44篇 |
2005年 | 40篇 |
2004年 | 38篇 |
2003年 | 32篇 |
2002年 | 15篇 |
2001年 | 19篇 |
2000年 | 27篇 |
1999年 | 30篇 |
1998年 | 22篇 |
1997年 | 14篇 |
1996年 | 18篇 |
1995年 | 12篇 |
1994年 | 28篇 |
1993年 | 29篇 |
1992年 | 17篇 |
1991年 | 23篇 |
1990年 | 22篇 |
1989年 | 14篇 |
1988年 | 13篇 |
1987年 | 14篇 |
1986年 | 18篇 |
1985年 | 18篇 |
1984年 | 14篇 |
1983年 | 12篇 |
1982年 | 18篇 |
1981年 | 11篇 |
1980年 | 8篇 |
1978年 | 1篇 |
1977年 | 4篇 |
1976年 | 1篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有1168条查询结果,搜索用时 46 毫秒
61.
Berta Otov Radka Vclavíkov Vlasta Danielov Jaroslava Holubov Marie Ehrlichov Stanislav Horský Pavel Sou
ek Petr imek Ivan Gut 《European journal of pharmaceutical sciences》2006,29(5):442-450
We investigated, whether the effects on paclitaxel, docetaxel or their combinations on T-cell lymphomas in Sprague-Dawley/Cub rats were mainly caused by their different efficiency or combination of different mechanism of action, or limited by metabolic inactivation by P450 enzymes or drug efflux caused by P-glycoprotein (P-gp). Docetaxel most effectively prolonged the survival of rats and the time of lymphoma appearance, inhibited their intravital size and weight after sacrifice. Paclitaxel was poorly effective and combined administration had intermediate effects. Blood levels of both drugs were similar. Repeated administration of paclitaxel, but not docetaxel, decreased its area under concentration, but the effect disappeared 6h after dosing and was not sufficient to explain lower effects of paclitaxel. The faster metabolism of docetaxel than paclitaxel in vitro did not limit its higher efficiency and repeated administration of paclitaxel did not induce its metabolism to decrease its blood levels sufficiently. Likewise, undetectable expression of P-gp protein in tumours could not explain lower effects of paclitaxel, which is a better substrate of P-gp. Docetaxel was three-fold more effective than paclitaxel against P388D1 lymphoma cell line, used as a model of the T-cell lymphoma and combined action was dominated by the effects of docetaxel. Thus, docetaxel was effective against T-cell lymphomas and may be a potential anticancer drug in similar indications. 相似文献
62.
M. Carafa L. Di Marzio C. Marianecci B. Cinque G. Lucania K. Kajiwara M.G. Cifone E. Santucci 《European journal of pharmaceutical sciences》2006,28(5):385-393
In an effort to enhance the oral bioavailability of scutellarin, ethyl, benzyl and N,N-diethylglycolamide ester of scutellarin were synthesized. The hydrolysis of the prodrugs follows first-order kinetics in aqueous solution, and produced a V-shaped pH profile. The N,N-diethylglycolamide ester is highly susceptible to enzymatic hydrolysis in human plasma (t1/2 ≈ 7 min) with a high stability in aqueous solution (t1/2 ≈ 16 day, pH 4.2). Compared with the solubility of scutellarin, the solubility of glycolamide ester was about ten times in pH 4.0 buffer, and about thirty five times in water. Its apparent partition coefficient increased significantly from −2.56 to 1.48. Glycolamide ester of scutellarin was chosen to investigate the intestinal metabolism and in vivo bioavailability. Degradation studies in the intestinal tract content and homogenates indicated intestinal metabolism before absorption was a crucial obstacle for the prodrug. N,N-Diethylglycolamide ester can be protected from the degradation in the intestinal lumen by an emulsion. A significant increase in the plasma AUC and Cmax of the prodrug emulsion was observed in rats, compared with that of the scutellarin–cyclodextrin complex (P < 0.01). The emulsion of N,N-diethylglycolamide ester produces a 1.58-fold enhancement in apparent bioavailability and 1.4-fold increase in the absolute bioavailability compared to the scutallarin–cyclodextrin complex. 相似文献
63.
目的对1%毛果芸香碱滴眼剂的两种不同剂型:1%毛果芸香碱水溶液和1%毛果芸香碱脂质体在兔眼房水中的药代动力学进行对比研究。方法 RP-HPLC 法采用 ODS—C_(18)柱,流动相:0.5%三乙胺的 KH_2PO_4(10 mmol/L)缓冲液(pH2.5)-乙腈(98:2,v/v);流速:1.0 ml/min,检测波长:215 nm;60只兔随机分为实验组和对照组,每组30只兔(60只眼),分别给实验组和对照组兔眼结膜囊滴入1%毛果芸香碱脂质体和1%毛果芸香碱水溶液各50μl,并于给药后5、10、30、40、60、90、120、180、240及360 min 时抽取3只兔(6眼)房水,用二氯甲烷提取房水中药物,用 RP-HPLC 法测定房水中的药物浓度。结果 RP-HPLC 法可以用于眼房水中毛果芸香碱的含量测定,毛果芸香碱浓度在0.1~20μg/ml 范围内线性良好,提取回收率68.10±1.9%。两种不同剂型毛果芸香碱滴眼后,不同时间点1%脂质体的房水药物浓度明显高于1%水溶液滴眼液的房水浓度(P=0.000~0.002),前者的药时曲线下面积是溶液的2.86倍,且1%脂质体滴眼剂在用药后6h 房水中仍可测出毛果芸香碱。结论毛果芸香碱脂质体可以明显提高毛果芸香碱的生物利用度,从而可能增强疗效,减少用药频率,值得进一步研究开发。 相似文献
64.
格列齐特的人体生物等效性研究 总被引:3,自引:0,他引:3
目的研究格列齐特的人体相对生物利用度和生物等效性。方法健康志愿者20例,随机双交叉单剂量口服格列齐特片的试验和参比制剂,剂量均为80 mg,剂间间隔为2周。分别于服药后60 h内多点抽取静脉血;用高效液相色谱法测定血浆中格列齐特的浓度。用DAS药动学程序计算相对生物利用度并评价两种制剂生物等效性。AUC(0-60),AUC(0-inf)和Cm ax经方差分析和双单侧t检验,tm ax进行秩和检验。结果单剂量口服试验和参比制剂后血浆中的格列齐特的Cm ax分别为(5.34±0.66)和(5.12±0.39)mg.L-1;tm ax分别为(4.30±0.92)和(4.15±0.67)h;AUC(0-60)分别为(92.67±12.12)和(89.82±13.33)mg.h.L-1;AUC(0-inf)分别为(96.36±12.87)和(93.37±13.83)mg.h.L-1。Cm ax、AUC(0-60)和AUC(0-inf)的90%可信区间分别为100.52%~107.56%,99.16%~107.97%和99.16%~107.97%。结论格列齐特试验制剂与参比制剂的人体相对生物利用度均为(104.5±15.5)%,两者具有生物学等效性。 相似文献
65.
目的:比较2种国产奥沙普秦肠溶片的相对生物利用度。方法:20名健康志愿者分别单剂量交叉口服受试制剂和对照制剂各400mg,采用高效液相色谱法测定人血浆中奥沙普秦浓度;采用3p97软件计算二者药动学参数,并计算生物利用度。结果:受试制剂和对照制剂的t1/2β分别为(73.468±24.354)、(73.556±24.406)h,tmax分别为(13.275±8.012)、(13.200±15.154)h,Cmax分别为(44.283±7.535)、(45.429±15.107)μg/ml,AUC0~Tn分别为(4471.792±1387.724)、(4234.328±1741.380)(μg.h)/ml,AUC0~inf分别为(5040.407±2092.744)、(4858.292±2423.656)(μg.h)/ml,均无统计学差异;受试制剂的相对生物利用度为(112.8±38.5)%。结论:2种国产奥沙普秦肠溶片具有生物等效性。 相似文献
66.
目的:研究健康受试者口服格列美脲口腔崩解片的人体药动学及相对生物利用度。方法:18名健康志愿者随机交叉单剂量口服格列美脲受试片与对照片4mg,采用柱前衍生化 HPLC-紫外法测定其血药浓度。结果:受试片与对照片的主要药动学参数 t_(max) 分别为(3.00±0.73)和(3.25±0.85)h,C_(max)分别为(313.1±99.3)和(303.2±104.5)μg·L~(-1),t_(1/2Ke)分别为(7.337±2.190)和(8.239±2.631)h,AUC_(0-t)分别为(1767.2±598.3)和(1714.1±528.3)μg·h·L~(-1),AUC_(0-∞)分别为(1956.3±598.1)和(1945.4±682.0)μg·h·L~(-1)。受试片的相对生物利用度为100.1%±18.2%。结论:两种片剂具有生物等效性。 相似文献
67.
目的:研究氟康唑胶囊受试制剂与参比制剂在健康志愿者体内的药代动力学和生物等效性。方法:18名健康男性受试者随机双周期交叉单剂量口服氟康唑胶囊受试制剂和参比制剂200 mg,用HPLC法测定氟康唑的血药浓度,求得有关药动学参数。结果:氟康唑胶囊受试制剂和参比制剂的AUC0~120 h分别为(224.977±39.361)和(211.212±36.221)mg/h.L-1,Cmax分别为(5.811±1.202)和(5.705±1.092)mg/L,Tmax分别为(1.056±0.466)和(1.375±0.884)h,t1/2分别为(32.559±5.072)和(30.162±7.257)h。受试制剂相对于参比制剂的生物利用度(F)为(107.41±14.79)%。氟康唑AUC0~120 h和Cmax经对数转换后双单侧t检验均P>0.05,受试制剂AUC0~120 h90%可信限度在参比制剂100.7%~112.6%内,Cmax 90%可信限度在参比制剂92.8%~111.1%区间内。结论:氟康唑胶囊的受试制剂与参比制剂具有生物等效性。 相似文献
68.
Sonderegger T Betticher DC Cerny T Lauterburg BH 《Cancer chemotherapy and pharmacology》2000,46(1):40-42
Purpose: Cladribine (2-chlorodeoxyadenosine, 2-CDA) is effective in the treatment of various lymphoproliferative disorders. In the
standard protocol the compound is administered by continuous intravenous (i.v.) infusion. In order to allow outpatient therapy
alternative modes of administration such as subcutaneous (s.c.) injection would be desirable. The aim of the present study
was to compare the pharmacokinetics of 2-CDA after i.v. and s.c. administration. Patients and methods: Nine patients received 0.1 mg/kg 2-CDA per 24 h on one occasion by continuous i.v. infusion and on another occasion as a
bolus subcutaneously. The concentrations of 2-CDA in the plasma and urine were determined by HPLC. Results: During i.v. infusion the concentration of 2-CDA in the plasma reached a plateau after 4–8 h, whereas with s.c. administration
almost ten times higher peak concentrations were reached within 20 to 60 min. A two-compartment model was fitted to the data
points whereby the goodness-of-fit statistics showed R
2 values of >0.98. The calculated rate of elimination, kelim, averaged 0.336 h−1 with s.c. and 0.397 h−1 with i.v. administration. The estimated volumes of distribution were 1.67 and 1.58 l/kg. The areas under the concentration
time curves (608 ± 65 pmol · h/ml after s.c. administration vs 571 ± 50 pmol · h/ml during i.v. infusion) and the urinary
excretion of 2-CDA in 24 h (4.75 ± 0.95 vs 3.55 ± 0.53 μmol/24 h) were similar in both groups, indicating identical bioavailability.
Conclusions: Although the pharmacokinetic profile of 2-CDA administered s.c. differs substantially from the profile of a continuous i.v.
infusion the areas under the plasma concentration time curves, the urinary excretion of unchanged drug and the estimated pharmacokinetic
variables were similar with both modes of administration, indicating that the different time-courses of the plasma concentration
did not influence the fraction metabolized or eliminated.
Received: 3 November 1999 / Accepted: 3 March 2000 相似文献
69.
Effects of orange juice on the pharmacokinetics of atenolol 总被引:3,自引:0,他引:3
Objective Fruit juices can significantly change the pharmacokinetics of several drugs. Our objective was to investigate the effect of orange juice on the pharmacokinetics of the beta-blocking agent atenolol.Methods In a randomized cross-over study with two phases and a washout of 2 weeks, ten healthy volunteers took either 200 ml orange juice or water thrice daily for 3 days and twice on the fourth day. On the morning of day 3, each subject ingested 50 mg atenolol with an additional amount of either 200 ml orange juice or water. The plasma concentrations of atenolol and the cumulative excretion of atenolol into urine were measured up to 33 h after its dosing. Systolic and diastolic blood pressures and heart rate were recorded in a sitting position before the intake of atenolol and 2, 4, 6, and 10 h after.Results Orange juice decreased the mean peak plasma concentration (Cmax) of atenolol by 49% (range 16–59%, P<0.01), and the mean area under the plasma atenolol concentration–time curve (AUC0-33 h) by 40% (range 25–55%, P<0.01). The time of the peak concentration (tmax) and the elimination half-life (t1/2) of atenolol remained unchanged by orange juice. The amount of atenolol excreted into urine was decreased by 38% (range 17–60%, P<0.01), but the renal clearance remained unaltered. The average heart rate was slightly higher during the orange juice+atenolol phase than during the water+atenolol phase.Conclusions Orange juice moderately interferes with the gastrointestinal absorption of atenolol. This food–drug interaction can be of clinical significance. 相似文献
70.
Borm PJ Cakmak G Jermann E Weishaupt C Kempers P van Schooten FJ Oberdörster G Schins RP 《Toxicology and applied pharmacology》2005,205(2):157-167
OBJECTIVE: The current study was designed to test the possible release and bioavailability of polycyclic aromatic hydrocarbons (PAHs) from a set of commercial carbon blacks (CBs) as well as the ability of these PAHs to form bulky DNA adducts. METHODS: In four commercial CBs (Printex 90, Sterling V, N330, Lampblack 101), leaching of PAH was examined through (1) release of parent PAHs in saline with or without surfactant, and (2) PAH adducts in lung epithelial cells (A549) or in rat lungs after exposure to two CBs (Printex 90, Sterling V) for 13 weeks (50 mg/m(3)). In vitro experiments were done with original and extracted particles, as well as organic extracts of CB in DMSO. As positive controls, B[a]P (0.03 microM) and a mixture of 16 PAHs (0.1 microM) were used. RESULTS: No leaching of PAHs was measured in saline or surfactant-containing saline. In vitro incubations with CB particles (30-300 microg/cm(2)) revealed no adduct spots except for Sterling V. However, the spot was not concentration dependent and remains unidentified. Lung DNA from rats after inhalation of Printex 90 or Sterling V showed no spots related to PAH-DNA adduct formation compared to sham-exposed rats. CONCLUSION: The results suggest that PAHs are very tightly bound to these CBs. Only using organic extracts or particles of low-surface Sterling V, with high PAH content, PAHs may become available to form PAH-DNA adducts. However, the in vitro conditions showing this effect will not be encountered in vivo and renders this mechanism in particle-induced lung cancer at in vivo exposures highly unlikely. 相似文献