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Morgan E. Gibbs Laura A. Wilt Kaitlyn V. Ledwitch Arthur G. Roberts 《Journal of pharmaceutical sciences》2018,107(7):1937-1947
P-glycoprotein (Pgp) is a multidrug resistance transporter that limits the penetration of a wide range of neurotherapeutics into the brain including opioids. The diphenylpropylamine opioids methadone and loperamide are structurally similar, but loperamide has about a 4-fold higher Pgp-mediated transport rate. In addition to these differences, they showed significant differences in their effects on Pgp-mediated adenosine triphosphate (ATP) hydrolysis. The activation of Pgp-mediated ATP hydrolysis by methadone was monophasic, whereas loperamide activation of ATP hydrolysis was biphasic implying methadone has a single binding site and loperamide has 2 binding sites on Pgp. Quenching of tryptophan fluorescence with these drugs and digoxin showed competition between the opioids and that loperamide does not compete for the digoxin-binding site. Acrylamide quenching of tryptophan fluorescence to probe Pgp conformational changes revealed that methadone- and loperamide-induced conformational changes were distinct. These results were used to develop a model for Pgp-mediated transport of methadone and loperamide where opioid binding and conformational changes are used to explain the differences in the opioid transport rates between methadone and loperamide. 相似文献
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北京市五所高校大学生对艾滋病/性病防治干预需求的定性研究 总被引:7,自引:0,他引:7
目的 探讨大学生对AIDS/STD预防教育/干预的看法和需求。方法 应用专题小组讨论(FGDs)方法。结果 14组FGDs结果表明:“恐艾症”和“认为AIDS离大学生很遥远”两种不同方向的认知在大学生中普遍存在;高校开展AIDS/STD防治干预活动是学生的共同愿望和需求;绝大多数学生主张干预内容应与性/生殖健康教育相结合,并强烈呼吁增加安全性行为(尤为避孕套知识和技能)教育的内容。干预活动易采用多种形式并用,以便具有不同特征的对象自主选择他们所喜欢的方式。另外,学生建议利用大众媒体创造良好的社会支持环境。结论 大学生对AIDS/STD预防教育的看法为有效地设计和实施教育项目提供了重要依据。在首都大学生中开展包括性教育在内的综合AIDS/STD防治干预活动势在必行。 相似文献
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Impact of sampling time deviations on the prediction of the area under the curve using regression limited sampling strategies 下载免费PDF全文
Sarem Sarem Fahima Nekka Iman Saad Ahmed Catherine Litalien Jun Li 《Biopharmaceutics & drug disposition》2015,36(7):417-428
The regression limited sampling strategy approach (R‐LSS), which is based on a small number of blood samples drawn at selected time points, has been used as an alternative method for the estimation of the area under the concentration–time curve (AUC). However, deviations from planned sampling times may affect the performance of R‐LSS, influencing related therapeutic decisions and outcomes. The aim of this study was to investigate the impact of different sampling time deviation (STD) scenarios on the estimation of AUC by the R‐LSS using a simulation approach. Three types of scenarios were considered going from the simplest case of fixed deviations, to random deviations and then to a more realistic case where deviations of mixed nature can occur. In addition, the sensitivity of the R‐LSS to STD in each involved sampling point was evaluated. A significant impact of STD on the performance of R‐LSS was demonstrated. The tolerance of R‐LSS to STD was found to depend not only on the number of sampling points but more importantly on the duration of the sampling process. Sensitivity analysis showed that sampling points at which rapid concentration changes occur were relatively more critical for AUC prediction by R‐LSS. As a practical approach, nomograms were proposed, where the expected predictive performance of R‐LSS was provided as a function of STD information. The investigation of STD impact on the predictive performance of R‐LSS is a critical element and should be routinely performed to guide R‐LSS selection and use. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
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目的 了解2005年广东省江门地区性病患者生殖支原体(Mg)感染情况,为性病防治工作提供依据.方法 采集84例性病门诊患者泌尿生殖道分泌物,用聚合酶链反应(PCR)技术检测生殖支原体脱氧核糖核酸(Mg DNA).结果 性病门诊患者Mg阳性率为17.86%,男性患者阳性率为21.21%,女性为5.56%,两者差异无统计学意义(x2=1.42,P>0.05).PCR对Mg标准菌株(G37)敏感度为10 ccu/ml.对10种其他支原体和10种相关微生物均未出现交叉反应.结论 江门地区性病患者中存在Mg感染并较为多见,在防治工作中应予重视. 相似文献
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《Women & health》2013,53(2):25-43
Findings are presented from an exploratory study of differences in the impact and mana ernent of heart disease between men and wornen aged 60 and over (N = 323). The sample consisted of ambulatory, non-institutionalized, cardiac patients who had agreed to participate in a self-management intervention study. Differences between men and women were found regarding sym tom experience, physical functioning, exercise compliance, use oPprescribed drugs, and physicianlclinic visits. Differences in emotional well-being and psychosocial functioning were not found; however, women reported more stress and limitat~on in the area of household management. Implications for future research and practice are discussed. 相似文献
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目的了解性病患者社会支持及社交回避与苦恼情况。方法采用领悟社会支持量表(PSSS)和社交回避与苦恼量表(SADS),对2005-2011年来门诊就诊的189名性病患者和176名健康人进行问卷调查。结果性病患者组SADS总分、回避因子、焦虑因子均高于健康对照组,差异有统计学意义(P〈0.01)。而性病患者组PSSS总分、家庭支持、朋友支持、其他支持得分低于健康组,差异有统计学意义(P〈0.01)。结论性病患者领悟到的社会支持低,在社交方面回避倾向及内心苦恼的感受较为严重 相似文献
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