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Masica AL Azie NE Brater DC Hall SD Jones DR 《British journal of clinical pharmacology》2000,50(3):273-276
AIMS: To study whether intravenous diltiazem, a calcium channel blocker commonly prescribed for hypertension and stable angina, is an inhibitor of the CYP3A enzymes by using oral lovastatin, an HMG Co-A reductase inhibitor, as a substrate. METHODS: Ten healthy volunteers were studied in a randomized two-way crossover design. The two arms were 1) administration of a 20 mg dosage of lovastatin orally and 2) administration of a 20 mg dosage of lovastatin orally 1 h after an intravenous loading dosage and constant infusion of diltiazem. Blood samples were collected up to 25 h in order to quantify lovastatin and diltiazem concentrations in the separated serum. Lovastatin and diltiazem concentrations were quantified by GC-MS and h.p.l.c., respectively. RESULTS: Intravenous diltiazem did not significantly affect the oral AUC, Cmax, t(1/2), or tmax of lovastatin. CONCLUSIONS: These data suggest that the interaction of lovastatin with diltiazem does not occur systemically and is primarily a first-pass effect. Thus, drug interactions with diltiazem may become evident when a patient is moved from intravenous to oral dosing. 相似文献
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Lack of pharmacokinetic interaction between the antimigraine compound, almotriptan, and propranolol in healthy volunteers 总被引:1,自引:0,他引:1
Fleishaker JC Sisson TA Carel BJ Azie NE 《Cephalalgia : an international journal of headache》2001,21(1):61-65
This study was designed to assess the pharmacokinetics of almotriptan, a 5-HT1B/1D agonist, when administered in the presence and absence of propranolol. Healthy male (n = 10) and female (n = 2) volunteers received (i) 80 mg propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii) 12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and urinary almotriptan concentrations were measured by high performance liquid chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters were assessed by analysis of variance (ANOVA). Statistically significant differences between treatments in area under the curve (AUC), clearance, and half-life were observed (P < 0.03), but these differences were < 7%. Ninety percent confidence interval analysis of log-transformed pharmacokinetic parameters showed that the treatments were equivalent. Adverse events were mild to moderate in intensity, and no treatment effects on vital signs were observed. The results show that propranolol has no effect on the pharmacokinetics of almotriptan. Concomitant administration of the two drugs is well tolerated. 相似文献
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Jackson T Chougule MB Ichite N Patlolla RR Singh M 《Cancer chemotherapy and pharmacology》2008,63(1):117-126
Purpose An antitussive plant alkaloid, Noscapine HCl (Nos) displays anticancer activity and has a safe pharmacological profile in
humans. The current study was aimed to investigate the in vitro and in vivo anti tumor activity of Nos to determine possible
mechanisms of anti tumor activity for treatment of non-small cell lung cancer (NSCLC).
Methods In vitro cytotoxicity of Nos was studied in H460 cells treated with different doses of Nos (10–160 μM) for 72 h and cell viability
was determined using crystal violet assay. Apoptosis in H460 cells was evaluated by TUNEL assay after treatment of cells for
72 h with 30 and 40 μM doses of Nos. For in vivo studies, female athymic Nu/nu mice were xenografted with H460 tumors and
on day 4 onwards Nos was administered orally at dose of 300, 450 and 550 mg/kg/day for 24 days. As a control, xenografted
tumors were separately treated with Docetaxel (10 mg/kg i.v. bolus on day 5, 11, 17, 23). The tumor volumes were measured
every five days. Expression of PARP, Bcl2, Bax, and caspase-3 families of proteins was measured by Western Blotting (WB), while TUNEL and Immunohistochemical methods
were utilized to determine DNA fragmentation and cleaved caspase-3 levels respectively.
Results Nos inhibited growth of H460 cells with the IC50 values of 34.7 ± 2.5 μM. Nos at 30 and 40 μM doses caused apoptosis as evidenced
by nuclear condensation in treated H460 cells. Nos caused 49, 65 and 86% reduction in the xenografted tumor volumes at a dose
of 300 (P < 0.05), 450 (P < 0.01), 550 mg/kg/day (P < 0.01), respectively, when compared to controls. Nos-dependent suppression of xenografted tumor growth involved up regulation
of PARP, Bax, caspase-3 and repression of Bcl2 expression. An increase in Bax/Bcl2 ratio suggests involvement of a mitochondrial mediated apoptotic processes. Our studies revealed a non significant (P > 0.05) increase in Bax/Bcl2 ratio with Nos at a dose of 300 mg/kg/day, while a significant (P < 0.001) increase in Bax/Bcl2 ratio was observed with Nos doses of 450 and 550 mg/kg/day. Further, Nos caused elevated apoptosis in tumor xenografts as
evidenced by enhanced expression of caspase-3 and positive TUNEL staining in regressed tumor tissues, thus suggesting induction
of apoptosis by mitochondrial pathway.
Conclusion Our studies suggest that potent antitumor activity of Nos against NSCLC cells. Oral administration of Nos showed significant
reduction in tumor volume in human non-small cell lung tumor xenograft in nude mice in a dose dependant manner. Thus, Nos
is a promising novel chemotherapeutic agent for the treatment of human lung cancer. 相似文献
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Patent medicine vendors (PMVs) are a ubiquitous feature of the informal health sector in Nigeria. A previous study on healthcare-seeking behaviour of persons with chronic cough in southern Nigeria found that over 60% of respondents chose the PMV as a healthcare provider of first instance. This study sought to determine the willingness and capability of PMVs to play a role in the national tuberculosis (TB)-control effort. Study sites were selected through a multi-stage sampling process. In total, 388 PMVs, 17 principal officers of PMV associations, and 17 community leaders were purposively selected. Sets of structured questionnaire were administered to the PMVs while information from the principal officers of PMV associations and community leaders was elicited through in-depth interviews and focus-group discussions (FGDs). Quantitative data were collated using the Epi Info software (version 6.04) and analyzed using the SPSS software (version 15). Most (90%) PMVs indicated that they would be ready to cooperate with the national TB-control programme, if trained. Seventy-three percent attended persons with prolonged cough in the course of their career. However, 48% did not know the cause of TB. Only 3% ever-attended a training session on TB control. Sixty-six percent completed at least 12 years of schooling with secondary school certificate. Eighty percent of the community leaders were happy with the work of PMVs. About two-thirds (65.6%) of the PMVs were male. The PMVs are positively disposed to playing roles in TB control. Given this positive disposition and their widespread acceptance in healthcare-delivery in the communities, they have potentials for playing a role in TB control in southern Nigeria. 相似文献
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Uchenna Eugenia Uzodinma Moses Onyemaechi Ede Ibiwari Caroline Dike Nkechi G. Onah Patience Enuma Obiweluozo Chimezie N. Onwurah Adaorah R. Onuorah Juliana Ngozi Ejiofor Collins Ikenna Ugwu Chijioke V. Amoke Sebastian O. Onah Benjamin C. Diara Christopher O. Okwor Olunwa Anthonia Aneke Anthonia N. Ngwoke Luke Chizoba Ezema Clara Odozi Ifelunni Ugwunna C. Nwachukwu Theresa O. Oforka Leonard C. Ilechukwu 《Medicine》2022,101(25)
Background:Most Christian parents living with children with low vision have reported to be experiencing psychological disturbances that are affecting the family health. As a result, the quality of family life is being impaired. The experience of parents catering for children with low vision is mainly influenced by psychosocial factors that could determine the quality of family life of such parents. This present study is to investigate the efficacy of rational emotive family health therapy in reducing poor quality of family life among Christian parents of children with low vision in Nsukka Catholic Dioceses.Method:This is a randomized pretest and posttest control trial. Participants were 88 parents of children living with low vision in Nsukka Catholic Dioceses, Nigeria. The power of the sample size was determined using Gpower statistical software. The participants in rational emotive family health therapy programme-group were exposed to a 12-session treatment programme whereas their counterparts in waitlisted control group did not receive anything. A family quality of life scale was utilized in assessing the participants. Data analyses were performed using repeated measures ANOVA.Results:It was found that rational emotive family health therapy had a significant positive effect on increasing quality of family life among the study participants compared to those in the waitlisted control group.Conclusion:This study contributed and validated the efficacy of rational emotive family health therapy in improving quality of family life among parents of children with low vision. 相似文献