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Rengasamy Padmanabhan Mohamed Shahul Hameed 《Virchows Archiv : an international journal of pathology》1985,408(1):61-73
Summary Single doses of cyclophosphamide were administered (IP) to groups of Wistar rats, on different days of gestation after neural tube closure (days 12–15) and fetuses were collected on day 20. A very large number of the fetuses treated during days 12–14 exhibited cranioschisis and exencephaly. Ethanol fixed, alizarin red stained specimens were observed for axial skeletal abnormalities. The exencephalic ones lacked ossified skulls. The basicranial bones were either under ossified or had undergone extensive fusion resulting in reduction in cranial volume. The basicraniovertebral angle was obtuse. The vertebral bodies and arches showed varying degrees of hypoplasia, fusion and/or agenesis. The development of ribs and sternebrae was also extensively affected. Treatment on day 15 did not induce exencephaly but the axial skeleton was hypoplastic. Wavy ribs were a remarkable feature of these fetuses. All exencephalic fetuses had subcutaneous haemorrhages; many of them were obviously oedematous. These data indicate that the susceptible period for induction of these anomalies does not stop at neuropore closure. 相似文献
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Abhishek Srivastava Vijender Panduga Ramanatha Saralaya Prabhakar K. R. Shahul Hameed Suresh Solapure 《Xenobiotica; the fate of foreign compounds in biological systems》2017,47(11):962-972
1.?During the course of metabolic profiling of lead Compound 1, glutathione (GSH) conjugates were detected in rat bile, suggesting the formation of reactive intermediate precursor(s). This was confirmed by the identification of GSH and N-acetylcysteine (NAC) conjugates in microsomal incubations.2.?It was proposed that bioactivation of Compound 1 occurs via the formation of a di-iminoquinone reactive intermediate through the involvement of the C-2 and C-5 nitrogens of the pyrimidine core.3.?To further investigate this hypothesis, structural analogs with modifications at the C-5 nitrogen were studied for metabolic activation in human liver microsomes supplemented with GSH/NAC.4.?Compounds 1 and 2, which bear secondary nitrogens at the C-5 of the pyrimidine core, were observed to form significant amounts of GSH/NAC-conjugates in vitro, whereas compounds with tertiary nitrogens at C-5 (Compound 3 and 4) formed no such conjugates.5.?These observations provide evidence that electron/hydrogen abstraction is required for the bioactivation of the triaminopyrimidines, potentially via a di-iminoquinone intermediate. The lack of a hydrogen and/or steric hindrance rendered Compound 3 and 4 incapable of forming thiol conjugates.6.?This finding enabled advancement of compound 4, with a desirable potency, safety and PK profile, as a lead candidate for further development in the treatment of malaria. 相似文献
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Shahul Hameed P Praveena Manjrekar Anandkumar Raichurkar Vikas Shinde Jayashree Puttur Gajanan Shanbhag Murugan Chinnapattu Vikas Patil Suresh Rudrapatana Sreevalli Sharma C. N. Naveen Kumar Radha Nandishaiah Prashanti Madhavapeddi D. Sriram Suresh Solapure Vasan K. Sambandamurthy 《ACS medicinal chemistry letters》2015,6(7):741-746
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Anderson John E. Ebrahim Shahul Floyd Louis Atrash Hani 《Maternal and child health journal》2006,10(1):101-106
Objectives: To assess the prevalence of risk factors for adverse pregnancy outcome during the preconception stage and during pregnancy, and to assess differences between women in preconception and pregnancy. Methods: Data from the 2002 and 2004 Behavioral Risk Factor Surveillance System, United States, were used to estimate the prevalence of selected risk factors among women 18–44 in the preconception period (women who wanted a baby in the next 12 months, and were not using contraception, not sterile and not already pregnant) with women who reported that they were pregnant at the time of interview. Results: Major health risks were reported by substantial proportions of women in the preconceptional period and were also reported by many pregnant women, although pregnant women tended to report lower levels of risk than preconception women. For example, 54.5% of preconception women reported one or more of 3 risk factors (frequent drinking, current smoking, and absence of an HIV test), compared with 32.0% of pregnant women (p < .05). The difference in the prevalence of these three risk factors between preconception and pregnancy was significant for women with health insurance (52.5% in preconception vs. 29.4% in pregnancy, p < .05), but not for women without insurance (63.4% vs. 52.7%, p > .05). Conclusions: Women appear to be responding to messages regarding behaviors that directly affect pregnancy such as smoking, alcohol consumption and taking folic acid, but many remain unaware of the benefits of available interventions to prevent HIV transmission and birth defects. Although it appears that some women reduce their risk for adverse pregnancy outcomes after learning of their pregnancy, the data suggest that a substantial proportion of women do not. Furthermore, if such change occurs it is often too late to affect outcomes, such as birth defects resulting from alcohol consumption during the periconception period. Preconception interventions are recommended to achieve a more significant reduction in risk and further improvement in perinatal outcomes. 相似文献
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Wong JW Yuen KH Nagappan S Shahul WS Ho SS Gan EK Toh WT 《The Journal of pharmacy and pharmacology》2003,55(2):193-198
We have evaluated the therapeutic equivalence of a beta-cyclodextrin-artemisinin complex at an artemisinin dose of 150 mg, with a commercial reference preparation, Artemisinin 250 at a recommended dose of 250 mg. One hundred uncomplicated falciparum malarial patients were randomly assigned to orally receive either beta-cyclodextrin-artemisinin complex (containing 150 mg artemisinin) twice daily for five days or the active comparator (containing 250 mg artemisinin) twice daily for five days. The patients were hospitalized for seven days and were required to attend follow up assessments on days 14, 21, 28 and 35. All patients in both treatment groups were cured of the infection and achieved therapeutic success. At day seven of treatment, all patient blood was clear of the parasites and the sublingual temperature of all patients was less than 37.5 degrees C. Moreover, the parasite clearance time in both treatment groups was similar, being approximately three days after initiation of treatment. Comparable plasma artemisinin concentrations were observed between patients in both treatment groups at 1.5 and 3.0 h, although slightly higher levels were obtained with patients in the beta-cyclodextrin-artemisinin complex-treated group. The beta-cyclodextrin-artemisinin complex at a dose of 150 mg artemisinin was therapeutically equivalent to 250 mg Artemisinin 250. Additionally, patients receiving beta-cyclodextrin-artemisinin complex showed less variability in their plasma artemisinin concentrations at 1.5 h post-dosing, which suggested a more consistent rate of drug absorption. 相似文献