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排序方式: 共有237条查询结果,搜索用时 106 毫秒
21.
22.
Effect of efavirenz treatment on the pharmacokinetics of nelfinavir boosted by ritonavir in healthy volunteers 下载免费PDF全文
la Porte CJ de Graaff-Teulen MJ Colbers EP Voncken DS Ibanez SM Koopmans PP Hekster YA Burger DM 《British journal of clinical pharmacology》2004,58(6):632-640
AIMS: A once-daily (q.d.) nucleoside-sparing regimen can prevent mitochondrial toxicity, overcome viral resistance and improve compliance. In the present study the effect of efavirenz on the pharmacokinetics and tolerability of once-daily nelfinavir/ritonavir was evaluated in healthy subjects. METHODS: This was a multiple-dose, open-label, single-group, two-period study in 24 healthy subjects. Each received from days 1-10 (period 1): 1875 mg nelfinavir plus 200 mg ritonavir q.d. with a 300-kcal snack. During days 11-20 (period 2) efavirenz 600 mg q.d. was added to the regimen. Blood samples were collected up to 24 h after dosing on days 10 (period 1) and 20 (period 2). High-performance liquid chromatography methods were used for the determination of the concentrations of all compounds. The main pharmacokinetic parameters were calculated using noncompartmental methods. RESULTS: All subjects completed the study. After the first period mean nelfinavir AUC(0-24 h), C(max) and C(24) were 49.6 mg h(-1) l(-1), 5.0 mg l(-1) and 0.37 mg l(-1), and the sum of nelfinavir plus its active metabolite M8 C(24) was 0.83 mg l(-1). The relative bioavailability, expressed as a geometric mean ratio (90% confidence interval) for nelfinavir AUC(0-24 h), C(max) and C(24) of period 2 compared with period 1 was: 1.30 (1.21, 1.40), 1.29 (1.19, 1.40) and 1.48 (1.32, 1.66). The sum of nelfinavir and M8 C(24) in period 2 was 0.99 mg l(-1), an increase of 19%. No serious adverse events occurred. CONCLUSIONS: The studied regimens were well tolerated. Nelfinavir/ritonavir given together with efavirenz resulted in a 48% higher mean C(24) concentration for nelfinavir, and the sum of nelfinavir and M8 C(24) concentrations was 0.99 mg l(-1). Efavirenz exposure in this study was similar to that reported previously, and therefore can be used effectively in combination with ritonavir and nelfinavir. 相似文献
23.
Bongiovanni M Chiesa E Riva A d'Arminio Monforte A Bini T 《International journal of antimicrobial agents》2003,22(6):630-631
The wide use of protease inhibitors (PI) as part of a highly active antiretroviral (HAART) regimen is associated with the development of several side effects. Among these, the development of avascular necrosis (AVN) of the bone is being reported more frequently and it has been related both to the use of PI and to HIV-1 infection itself. We report here a case of AVN of the bone in a patient taking the new PI lopinavir (LPV)/ritonavir (RTV) as part of a HAART regimen. 相似文献
24.
Shibata N Kageyama M Kishida T Kimura K Yoshikawa Y Kuwahara T Toh J Shirasaka T Takada K 《Biopharmaceutics & drug disposition》2003,24(8):335-344
Throughout therapeutic drug monitoring of human immunodeficiency virus (HIV) protease inhibitors in HIV-infected patients, it was found that plasma concentrations of saquinavir (SQV) were reduced in patients who had a habit of alcohol intake during double protease therapy with SQV and ritonavir (RTV). This study confirmed the pharmacokinetic profiles of SQV during ethanol intake in rats. After oral administration of SQV alone (20 mg/kg) in rats prepared by free access to 15% ethanol solution for 14 days (day 14 rats), the area under the concentration vs time curves (AUC) showed a significant decrease (p<0.01) in comparison with control rats from 0.78+/-0.10 to 0.38+/-0.03 microg h/ml. For intravenous administration of SQV alone (5 mg/kg) to day 14 rats, the total body clearance increased significantly by 1.4-fold (p<0.05), whereas for intracolonic administration of SQV alone, no significant differences in the values of pharmacokinetic parameters were found between control and day 14 rats. With RTV, which has the strongest inhibitory effect on the CYP3A enzyme of the current HIV protease inhibitors, the AUC values of SQV at RTV doses of 2 and 20 mg/kg in day 14 rats also decreased significantly (p<0.01) from 1.30+/-0.06 to 0.57+/-0.05 microg h/ml and from 17.63+/-1.66 to 4.18+/-0.94 microg h/ml, respectively, indicating that the degree of the decrease of AUC values after oral administration with RTV after ethanol intake was larger than the mono-therapy with SQV. This study showed that ethanol-intake decreases the bioavailability of SQV after oral administration alone or with RTV. These observations provide useful information for the treatment of HIV-infected patients when they receive a combination therapy with SQV and RTV, and arouse attention for the effects of alcohol intake. 相似文献
25.
Role of P-Glycoprotein on the CNS Disposition of Amprenavir (141W94), an HIV Protease Inhibitor 总被引:7,自引:0,他引:7
Polli Joseph W. Jarrett Jeanne L. Studenberg Scott D. Humphreys Joan E. Dennis Steven W. Brouwer Kenneth R. Woolley Joseph L. 《Pharmaceutical research》1999,16(8):1206-1212
Purpose. To determine the role of P-glycoprotein (Pgp) on the CNS penetration of the HIV protease inhibitor (PI) amprenavir (141W94) and to test the hypothesis that co-administration of a second HIV PI (ritonavir) could enhance amprenavir's brain penetration in vivo.
Methods. Pgp-mediated efflux was investigated in vitro with Caco-2 cells and in vivo by whole-body autoradiography (WBA). 'Genetic'mdrla/lbdouble knockout mice, 'chemical' Pgp knockout mice generated by administration of the Pgp inhibitor GF120918, and mice pretreated with ritonavir were used in WBA studies to investigate the effects of Pgp modulation on the CNS penetration of amprenavir.
Results. Amprenavir, indinavir, ritonavir, and saquinavir had 2-to 23-fold higher transport rates from the basolateral to apical direction than from the apical to basolateral direction across Caco-2 monolayers. Incubation with GF 120918 negated this difference, suggesting that the efflux was Pgp-mediated. WBA studies demonstrated a 13- and 27-fold increase in the brain and a 3.3-fold increase in the CSF concentrations of amprenavir in mice pretreated with GF120918 and in mdrla/lbdouble knockout mice. In contrast, pretreatment with ritonavir did not alter the CNS exposure of amprenavir.
Conclusions. These results provide evidence that amprenavir and other HIV PIs are Pgp substrates and that co-administration of a specific Pgp inhibitor will enhance amprenavir's CNS penetration in vivo. These results will have an important therapeutic impact in the treatment of AIDS dementia. 相似文献
26.
Urien S Firtion G Anderson ST Hirt D Solas C Peytavin G Faye A Thuret I Leprevost M Giraud C Lyall H Khoo S Blanche S Tréluyer JM 《British journal of clinical pharmacology》2011,71(6):956-960
AIMS
Because of immature hepatic metabolism, lopinavir could present specific pharmacokinetics in the first weeks of life. We aimed at determining the optimal dosing regimen in neonates and infants weighing 1 to 10.5 kg.METHODS
Lopinavir/ritonavir (LPV/r) pharmacokinetics were studied in 96 infants using a population approach.RESULTS
A one-compartment model described LPV/r pharmacokinetics. Normalized to a 70 kg adult using allometry, clearance (CL/F) and distribution volume (V/F) estimates were 5.87 l h−1 70 kg−1 and 91.7 l 70 kg−1. The relative bioavailabilty, F, increased with post-menstrual age (PMA) and reached 50% of the adult value at 39.7 weeks.CONCLUSIONS
Size and PMA explained some CL/F and V/F variability in neonates/infants. Based upon trough concentration limitations, suggested LPV/r dosing regimens were 40 mg 12 h−1, 80 mg 12 h−1 and 120 mg 12 h−1 in the 1–2 kg, 2–6 kg and 6–10 kg group, respectively. 相似文献27.
Smith CJ Phillips AN Youle MS Sabin CA Lampe FC Tsintas R Tyrer M Johnson MA 《HIV medicine》2007,8(1):55-63
Objective
To describe outcomes in patients starting first‐line antiretroviral regimens including lopinavir/ritonavir (LPV/r) in a routine clinic setting.Methods
Previously naïve patients starting LPV/r‐containing antiretroviral therapy were included in the study. Virological failure was defined as the first of two viral loads >500 HIV‐1 RNA copies/mL more than 6 months after starting LPV/r. Cumulative percentages experiencing virological failure were calculated using Kaplan–Meier methods.Results
A total of 195 individuals had a median follow‐up time of 1.7 years. At 48 weeks, 87.9, 77.4 and 71.6% of patients with pretreatment CD4 counts of <50, 50–200 and >200 cells/μL, respectively, remained on LPV/r. By 48, 72 and 96 weeks, 2.2, 3.0 and 5.0% of patients, respectively, had experienced virological failure, ignoring treatment changes but censoring follow‐up at discontinuation of all antiretrovirals; these percentages became 24.0, 33.7 and 42.3% when LPV/r discontinuation was considered as virological failure. Censoring those who stopped LPV/r with a viral load <50 copies/mL and considering as virological failures those who stopped LPV/r with a viral load >50 copies/mL gave 12.1, 14.6 and 17.0% virological failure at 48, 72 and 96 weeks, respectively. Median CD4 count increases at 24, 48 and 72 weeks were 167, 230 and 253 cells/μL, respectively.Conclusions
Few patients experienced virological failure whilst on a LPV/r‐based regimen, although it was not uncommon for patients in our clinic with higher baseline CD4 counts to discontinue LPV/r.28.
29.
30.
《Expert review of anti-infective therapy》2013,11(7):801-805
With the introduction of combination antiretroviral therapy (cART), there have been dramatic reductions in mortality and morbidity of HIV-1-infected patients. Protease inhibitor-based regimens remain a cornerstone of cART owing to their potency and high genetic barrier to resistance. The comparison of atazanavir/ritonavir in naive subjects in combination with tenofovir–emtricitabine versus lopinavir/ritonavir in combination with tenofovir–emtricitabine to assess safety and efficacy (CASTLE) study is a noninferiority trial in which the efficacy, safety and tolerability of atazanavir–ritonavir and lopinavir–ritonavir were compared in antiretroviral therapy-naive patients. The aim of this paper is to review the CASTLE study and the role of atazanavir–ritonavir as an initial treatment in HIV-1-infected patients. 相似文献