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1.
The pandemic of coronavirus disease 2019 (COVID-19) is a global health emergency that poses a significant threat to world people’s health. This outbreak causes major challenges to healthcare systems. Given the lack of effective treatments or vaccine for it, the identification of novel and safe drugs against COVID-19 infection is an urgent need. Angiotensin-converting enzyme 2 (ACE2) is not only an entry receptor of the SARS-CoV-2 virus, the virus that causes COVID-19, but also can protect from lung injury. In this view, we highlighted potential approaches to address ACE2-mediated SARS-CoV-2 virus, including 1) delivering an excessive soluble form of ACE2 (recombinant human ACE2: rhACE2) and 2) inhibition of the interaction between SARS-CoV-2 virus and ACE2 by some compounds with competitive effects (morphine and codeine). Further clinical trials in this regard can reveal a more definite conclusion against the COVID-19 disaster.  相似文献   
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Opium poppy has important medical, socioeconomic, forensic and political implications. More than 80 benzylisoquinoline alkaloids have been described, many of them with relevant therapeutic properties such as morphine, codeine, papaverine and noscapine. Heroin, a semi-synthetic drug produced from morphine is a worldwide serious cause of morbidity and mortality. Heroin dependence is complex phenomenon with environmental and genetic influence, and several biomarkers of exposure have been proposed. This work aims to review the metabolism and metabolomics of opiates with particular interest on their relevance as potential clinical and forensic antemortem and postmortem biomarkers. It is known that the heroin is mainly a prodrug that is rapidly deacetylated in blood to its active metabolite, 6-acetylmorphine, which is then subsequently slowly deacetylated to morphine. Therefore, 6-acetylmorphine has been used as the main target metabolite to prove heroin abuse in clinical, but mostly in forensic routine. Nevertheless, its applicability is limited due to the reduced detection window. Therefore, morphine (and its metabolites morphine-3-glucuronide and morphine-6-glucuronide), codeine, codeine-6-glucuronide, 6-acetylcodeine, noscapine (and its metabolites meconine, desmethylmeconine, and cotarnine), papaverine (and its metabolites 6-desmethylpapaverine, hydroxypapaverine, dihydroxypapaverine, 6-desmethylpapaverine-glucuronide) and thebaine (and acetylthebaol and the non-acetylated analog thebaol) have been additionally recommended to obtain the most reliable results possible. More recently, the identification by metabolomics analysis of several endogenous compounds offered an alternative approach of significant importance to uncover toxic effects. Profound alterations in the neurotransmitters levels and energy and amino acid metabolism have been reported with l-tryptophan, 5-hydroxytryptamine and 5-hydroxyindoleacetate being suggested as potential non-specific biomarkers of long-term heroin addiction. These endogenous metabolic profiles and exogenous components that together comprise the exposome will certainly help to uncover metabolic disturbances and patterns that may be associate to addiction with relevant clinical and forensic implications.  相似文献   
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Abstract

Samples of codeine resinate consisting of a carboxylic cation exchanger (as a polymeric carrier) and codeine (as a drug) were coated with poly(alkyl α-cyanoacrylates) by suspending and stirring wet resinate beads in a toluene solution of the monomer. Methyl, ethyl and n-butyl α-cyanoacrylates were used as monomers. Each coated material released codeine more slowly than the non-coated. The data obtained confirmed that water promoted the polymerization of alkyl α-cyanoacrylates, which proceeded at the surface of the wet resinate beads. The rate of codeine release depended on the type of monomer used for coating, the monomer/resinate feed ratio and the plymerization time.  相似文献   
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目的通过绝对定量分析健康青年人服用磷酸可待因后双侧前额叶及海马代谢物浓度变化,为下一步研究青年人可待因慢性成瘾机制提供前期实验数据参考。材料与方法正常健康青年志愿者20名,男10名,女10名,年龄18~30岁,平均(24.9±1.9)岁,均为右利手,无神经、精神疾病病史。采用GE 1.5 T Signa HDX超导MR扫描仪,单体素1H-MRS PRESS序列,TR 3000 ms,TE 30 ms,矩阵256×128,NEX为1,感兴趣区置于双侧前额叶及双侧海马,大小2 cm×2 cm×2 cm,采集服药前及口服60 mg磷酸可待因后1.0~2 h内的实验数据,利用LCModel软件对采集的数据进行后处理及定量,用SPSS19.0配对样本t检验进行统计学分析。结果服用磷酸可待因后左前额叶脑代谢物发生改变,甘油磷酸胆碱(GPC)浓度增加0.254 mmol/L、肌醇(Ins)浓度下降0.988 mmol/L,差异有统计学意义(n=13,P0.05;n=12,P0.05);右前额叶、双侧海马的代谢物浓度改变无统计学差异。结论口服磷酸可待因能引起左前额叶代谢物的改变,GPC浓度上升与Ins浓度下降可能与急性用药后前膜递质释放减少有关。  相似文献   
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We aimed to evaluate the efficacy and safety of oxycodone/acetaminophen (O/A) and codeine/acetaminophen (C/A) vs. conventional therapy (CT) without opioids in older women suffering from osteoarthritis (OA)-related pain, sub-optimally responsive to prior conventional treatments. We performed a 6 week, randomized, single blind, controlled study in three nursing homes. We enrolled 154 women with painful OA. They were assigned to treatment with O/A (n = 52) and C/A (n = 52) vs. CT (n = 50). We evaluated at baseline and at week 6: average pain in the last week (mean pain, MeP), pain at rest (RP), pain in movement (MP) (numeric rating scale, NRS); depressive symptoms (Beck Depression Inventory-II, BDI-II); functional status (activities of daily living, ADL) and cognitive status (mini mental state evaluation, MMSE). We considered the adverse events (AEs) in the study period. At week 6, MeP, RP and MP were significantly reduced in all three groups (p < 0.001); compared to CT, O/A and C/A were associated with greater reductions in MeP (p < 0.001 and p = 0.004, respectively), in RP (p = 0.028 and p = 0.032, respectively) in MP (p < 0.001 and p = 0.002, respectively) and with significant improvement in BDI-II score (p = 0.05 and p = 0.04, respectively) and ADL value (p = 0.04 and p = 0.05, respectively). AE rates did not differ between groups.  相似文献   
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目的:氯芬待因片含量测定的方法学研究.方法:色谱柱为Symmetry C18(5μm,250 mm×4.6mm);流动相为乙腈-0.4%乙酸铵水溶液-三乙胺(30∶70∶0.2);检测波长250 nm;流速1.0 mL/min.结果:双氯芬酸钠在0.050~2.500 mg/mL浓度范围内线性关系良好(r=0.999 ...  相似文献   
9.
Summary The polymorphic cytochrome P-450 DB1 (P-450 IID6) is responsible for the O-demethylation of codeine to morphine by human liver microsomes. The influence of P-450 DB1 variable activity on the bioactivation of codeine in vivo to morphine and on its analgesic effect was investigated in phenotyped healthy volunteers — 7 extensive [EM] and 1 poor [PM] metabolizer of debrisoquine. After pretreatment with oral placebo or quinidine sulphate 50 mg, codeine phosphate 100 mg or placebo were administered orally according to a double-blind randomized crossover design.In EM subjects the plasma morphine Cmax was 17.9 nmol/l, whereas virtually no morphine was detectable after quinidine pretreatment (1.5 nmol/l), and in the PM subject (0.60 nmol/l). In EM codeine significantly increased subjective (VAS) and objective (R-III reflex) pain thresholds in response to selective transcutaneous nerve stimulation, whereas no significant analgesia was detected after placebo, or after codeine with quinidine pretreatment, or in the PM. In PM of genetic origin, or due to environmental alteration of the phenotypic expression (i.e. drug interaction), codeine is not activated into morphine and is an inefficient analgesic.Presented in part at the 2nd International Congress on Cancer Pain, New York, N.Y., July 1988, and at the Nineteenth Annual Meeting of the American Society For Clinical Pharmacology and Therapeutics, Nashville, Tennessee, March 1989  相似文献   
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目的:建立气相色谱法同时测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱四种成分含量的方法。方法:试样用乙酸乙酯振摇提取,色谱柱为100%二甲基聚硅氧烷固定液的毛细管柱,柱温从100℃程序升温至270℃,保持20 min,检测器为 FID。结果:薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱在各自测定范围内有良好线性关系,各成分平均回收率(n=6)在96.76%~113.34%,RSD<6.0%。结论:本方法准确可靠,重现性好,可有效地控制强力枇杷露的质量。  相似文献   
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