全文获取类型
收费全文 | 376篇 |
免费 | 23篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 14篇 |
妇产科学 | 8篇 |
基础医学 | 37篇 |
口腔科学 | 9篇 |
临床医学 | 42篇 |
内科学 | 65篇 |
皮肤病学 | 1篇 |
神经病学 | 7篇 |
特种医学 | 19篇 |
外科学 | 28篇 |
综合类 | 11篇 |
预防医学 | 39篇 |
药学 | 111篇 |
肿瘤学 | 13篇 |
出版年
2022年 | 6篇 |
2021年 | 5篇 |
2018年 | 1篇 |
2017年 | 4篇 |
2016年 | 3篇 |
2015年 | 3篇 |
2014年 | 5篇 |
2013年 | 8篇 |
2012年 | 7篇 |
2011年 | 12篇 |
2010年 | 5篇 |
2009年 | 15篇 |
2008年 | 10篇 |
2007年 | 14篇 |
2006年 | 5篇 |
2005年 | 6篇 |
2004年 | 9篇 |
2003年 | 13篇 |
2002年 | 12篇 |
2001年 | 19篇 |
2000年 | 11篇 |
1999年 | 13篇 |
1998年 | 14篇 |
1997年 | 11篇 |
1996年 | 5篇 |
1995年 | 12篇 |
1994年 | 10篇 |
1993年 | 9篇 |
1992年 | 13篇 |
1991年 | 7篇 |
1990年 | 16篇 |
1989年 | 10篇 |
1988年 | 13篇 |
1987年 | 13篇 |
1986年 | 22篇 |
1985年 | 9篇 |
1984年 | 9篇 |
1983年 | 7篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 1篇 |
1979年 | 6篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1972年 | 2篇 |
1971年 | 4篇 |
1969年 | 3篇 |
排序方式: 共有404条查询结果,搜索用时 375 毫秒
1.
T B Vree Y A Hekster M W Tijhuis E F Termond J F Nouws 《Biopharmaceutics & drug disposition》1986,7(3):239-252
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes. 相似文献
2.
3.
Akosua N.J.A. de Groot Pieter W.J. van Dongen Tom B. Vree Tom K.A.B. Eskes 《European journal of obstetrics, gynecology, and reproductive biology》1995,60(2):101-107
Objective: To study the pharmacodynamic and pharmacokinetic properties of oral and intravenous methylergometrine upon uterine motility during menstruation. Study-design: Intra-uterine pressure was measured in six volunteers with a fluid-filled sponge-tipped catheter during menstruation. Methylergometrine was given orally (0.5 mg) or intravenously (0.2 mg) in a cross-over design. Results: After intravenous administration, a fast increase of the frequency of uterine contractions and basal tone occurred with a decrease of amplitude, lasting at least 30 min. Oral administration had a late and less marked effect on uterine motility. An intravenous dose administered 24 h after an oral dose had no effect on uterine motility. Pharmacokinetic data, such as the maximum plasma concentration (Cmax), the time at which Cmax is reached (tmax) and the half-life of absorption (t1/2abs) also demonstrated large individual variations after oral administration. Conclusion: Oral administration of methylergometrine had an unpredictable and late effect on uterine motility on the menstruating uterus, probably due to an unpredictable bioavailability, in contrast with the fast and predictable effect after intravenous administration. 相似文献
4.
W J Wijnands J F Trooster P C Teunissen H A Cats T B Vree 《Drug metabolism and disposition》1990,18(6):954-957
The pharmacokinetics of a single iv dose of 10 mg diazepam and the renal excretion of its metabolites resulting from N-demethylation and C-3-hydroxylation were investigated in 10 healthy volunteers when diazepam was administered alone and on day 3 of administration of the fluoroquinolone ciprofloxacin (500 mg twice per day). No significant changes in the diazepam half-life, its volume of distribution, the total body clearance, or the renal clearance were observed. In addition, the renal excretion of the metabolites desmethyldiazepam, 3-hydroxydiazepam (temazepam), and 3-hydroxydesmethyldiazepam (oxazepam) were not altered by ciprofloxacin co-medication. These data demonstrate that in a 500 mg twice per day oral dosage, ciprofloxacin does not influence the metabolic clearance of diazepam in young healthy volunteers. 相似文献
5.
In vitro effects of sulfadiazine and its metabolites alone and in combination with pyrimethamine on Toxoplasma gondii. 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Antimicrobial agents and chemotherapy》网站下载免费的PDF全文](/ch/ext_images/free.gif)
E Schoondermark-van de Ven T Vree W Melchers W Camps J Galama 《Antimicrobial agents and chemotherapy》1995,39(3):763-765
Sulfadiazine and the metabolites N4-acetyl-sulfadiazine, 4-OH-sulfadiazine, 5-OH-sulfadiazine, 5-OH-glucuronide-sulfadiazine, and 5-OH-sulfate-sulfadiazine were tested separately and in combination with pyrimethamine for the inhibitory activity on Toxoplasma gondii growth in vitro. Except for N4-acetyl-sulfadiazine, all sulfa compounds possessed anti-Toxoplasma activity. The addition of 0.05 micrograms of pyrimethamine per ml, a concentration which in itself is not inhibitory, potentiated the microbial activity of sulfadiazine and its metabolites 100 fold. 相似文献
6.
Huisman JA; Paulussen RJ; Geurts TB; Odink J; Rekers H 《Human reproduction (Oxford, England)》1997,12(1):34-38
The objective was to demonstrate bioequivalence between s.c. and i.m.
administration of Humegon (FSH/LH ratio 1:1) and Normegon (FSH/LH ratio
3:1). In two randomized, single-centre, cross-over studies, 18 healthy
volunteers on each formulation were assigned to one of the two
administration sequences. Subjects were given single doses of one of the
above gonadotrophins after endogenous gonadotrophin production had first
been suppressed using high-dose oral contraceptive. Subsequently, rate
(Cmax, tmax) and extent (AUC) of absorption of follicle stimulating hormone
(FSH) and luteinizing hormone (LH) were determined for 14 days. For Cmax
and AUC, analysis of variance (ANOVA) was performed on log-transformed data
and for tmax ANOVA was performed on ranks. Intramuscular and s.c.
injections of Humegon were bioequivalent with respect to the main
pharmacokinetic parameters, being AUC and Cmax of FSH absorption.
Intramuscular and s.c. injections of Normegon were bioequivalent with
respect to the AUC of FSH and not bioequivalent with respect to the Cmax of
FSH. For tmax of FSH as well as for most LH variables of both preparations,
bioequivalence could not be proven due to the high intra- and
interindividual variability and/or concentrations being close to the
detection limit. Thus, the main pharmacokinetic FSH variables after i.m.
and s.c. administration of Humegon and Normegon were bioequivalent.
相似文献
7.
M. Martea Y. A. Hekster T. B. Vree A. J. Voets J. H. M. Berden 《Pharmacy World & Science》1987,9(2):110-116
Cefradine and co-trimoxazole pharmacokinetics were studied in a patient with peritonitis that complicated continuous ambulatory peritoneal dialysis (CAPD). Concentrations in the plasma reached after oral administration of 500 mg cefradine four times daily and 400/80 mg co-trimoxazole four times daily were for cefradine 100g/ml, for trimethoprim 15g/ml, and for sulfamethoxazole 100/ml, respectively. In the dialysate concentrations were reached of 35–70/ml cefradine, 2–5/ml trimethoprim and 8–17g/ml sulfamethoxazole. The values for sulfamethoxazole are regarded too low to be clinically effective. Half-lives protein binding values and CAPD clearances are presented. Low CAPD clearances were obtained during the night and high values during the day. The dosage yielded too high plasma trimethoprim concentrations, while sulfamethoxazole dialysate concentrations were too low. It seems questionable therefore whether co-trimoxazole can be used orally for the treatment of CAPD peritonitis. 相似文献
8.
Zbigniew Zylicz D. J. Theo Wagener Marina Garzotto Tom B. Vree Eppo van der Kleijn Leon A. G. M. van den Broek Harry C. J. Ottenheijm 《Investigational new drugs》1990,8(1):25-32
Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 was 0.2 hours (12 minutes) and t1/2 was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics. 相似文献
9.
Miguel M. Alvarez Ferrero Tom B. Vree Eleonora W J. Van Ewijk-Beneken Kolmer Tom J. J. H. Slooff 《Biopharmaceutics & drug disposition》1994,15(7):599-608
- (i) The objective was to determine the range of bone levels of cefuroxime and flucloxacillin achieved after one intravenous (IV) administration of different dosages of cefuroxime and flucloxacillin.
- (ii) Six groups of five patients participated in the study. The first three groups (A–C) received respectively 1500 mg, 1000 mg, and 500 mg cefuroxime intravenously and the second three groups (D–F) received 2000 mg, 1500 mg, and 1000 mg flucloxacillin intravenously.
- (iii) Parenteral administration of cefuroxime and flucloxacillin resulted in measurable bone concentrations in all patients.
- (iv) Large inter-individual variation in bone concentration was observed.
- (v) The bone concentrations of IV cefuroxime were higher (1500 mg, p = 0.0057; 1000 mg, p = 0.0260) than those of flucloxacillin. The bone concentrations of cefuroxime and flucloxacillin were dose dependent.
10.
Lack of enteral nutrition during critical illness is associated with profound decrements in biliary lipid concentrations. 总被引:2,自引:0,他引:2
J M de Vree J A Romijn K S Mok L M Mathus-Vliegen C P Stoutenbeek J D Ostrow G N Tytgat H P Sauerwein R P Oude Elferink A K Groen 《The American journal of clinical nutrition》1999,70(1):70-77
BACKGROUND: Food in the intestine drives the enterohepatic circulation of bile components. OBJECTIVE: We investigated whether parenteral or enteral delivery of nutrients alters serum and biliary lipids in critically ill patients. DESIGN: Eight intensive care unit (ICU) patients who had received >/= 5 d of total parenteral nutrition (TPN) were compared with 8 ICU patients who had fasted for >/=5 d. Both groups were studied before and after 5 d of enteral nutrition (EN). Each patient served as his or her own control. Duodenal bile was analyzed for biliary lipid content and serum lipids were determined simultaneously. Duodenal bile samples from 18 healthy persons served as controls. RESULTS: Bile salt concentrations in all ICU patients were 17% of control values before EN (P < 0.005) and 34% of control values after 5 d of EN (P < 0.005). Phospholipid concentrations were 12% of control before EN (P < 0. 0005) but increased almost 4-fold after EN (P < 0.0005). Biliary cholesterol concentrations were 20% of control values before EN (P < 0.001) and did not improve afterward. No difference in bile composition was observed between fasted ICU patients and those who received TPN. The inverse correlation between the severity of illness and biliary lipid concentrations observed before EN disappeared with enteric stimulation. The low serum concentrations of HDL cholesterol and apolipoprotein A-I increased significantly with EN in all ICU patients. CONCLUSION: Lack of EN during critical illness was associated with profound decrements in biliary lipid concentrations that normalized partially after 5 d of EN. We hypothesize that loss of enteric stimulation in ICU patients impairs hepatic lipid metabolism. 相似文献