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严清明  王婕 《西南军医》2011,13(4):769-770
目前部分军队医院使用的数据库版本是ORACLE8I,随着医院业务的逐渐扩大和应用系统的需求,老版本数据库日益凸现"衰老",数据库升级已迫在眉睫。ORACLE10G有以下的新特点:FLASHBACK(闪回)功能,可以轻松的将数据库还原到某一个点上,轻松的将删除的表还原;自动工作负荷存储库  相似文献   
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Male wild (Cavia aperea) and domestic (C. porcellus) guinea pigs were tested in two-bottle choice tests for preferences between glucose solutions of different concentrations and de-ionized water. Wild males showed significant preferences for concentrations between 0.025 and 0.4 M glucose while domestic males preferred only the 0.2 M glucose solution to de-ionized water. C. aperea males also consumed significantly greater volumes of liquid per kg body wt.34 during the glucose tests than did the C. porcellus males. These comparative results contrast sharply with those obtained by other authors with wild and domestic Norway rats.  相似文献   
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刘茜  刘艳芳  赵辉  刘洋  张旭  王书典 《中国药学杂志》2012,47(14):1139-1142
 目的 比较氨氯地平、氯沙坦及其代谢产物EXP3174 3种物质在单、复方制剂给予Beagle犬时的药动学差别。方法 采用LC-MS/MS法,分别测定6只Beagle犬交叉口服单方或复方制剂后血浆中氨氯地平、氯沙坦及其代谢产物EXP3174的浓度,应用DAS软件计算药动学参数。结果 ①单方和复方制剂中氯沙坦主要药动学参数:tmax(1.36±0.46)和(1.03±0.27)h;ρmax(905±477)和(1 009±440)ng·mL-1;AUC0-t(1 556±696)和(1 601±432)ng·h·mL-1。②单方和复方制剂中EXP3174的主要药动学参数:tmax(1.67±0.41)和(1.42±0.38)h;ρmax(69.2±48.1)和(47.1±14.6)ng·mL-1;AUC0-t(191±120)和(142±80.6)ng·h·mL-1。③单方和复方制剂中氨氯地平的主要药动学参数:tmax(2.75±0.61)和(3.00±0.95)h;ρmax(38.5±14.9)和(33.8±8.05)ng·mL-1;AUC0-t(467±163)和(438±141)ng·h·mL-1。结论 单、复方苯磺酸氨氯地平/氯沙坦钾片在Beagle犬体内的主要有效成分氨氯地平、氯沙坦及其代谢产物EXP3174的各药动学参数均不存在显著性差异。  相似文献   
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BACKGROUND AND PURPOSE: Whereas some angiotensin II (Ang II) type 1 receptor blockers (ARBs) produce surmountable antagonism of AT(1) receptors, others such as olmesartan and telmisartan display varying degrees of insurmountability. This study compared the molecular interactions of olmesartan and telmisartan with the human AT(1) receptor, using well characterised in vitro methods and model systems. EXPERIMENTAL APPROACH: CHO-K1 cells that stably express human AT(1) receptors (CHO-hAT(1) cells) were used in several pharmacological studies of olmesartan and telmisartan, including direct radioligand binding and inhibition of Ang II-induced inositol phosphate (IP) accumulation. KEY RESULTS: Both ARBs were found to be competitive antagonists that displayed high affinity, slow dissociation, and a high degree of insurmountability for the AT(1) receptor (the latter greater with olmesartan). Their receptor interactions could be described by a two-step process with the initial formation of a loose complex (IR) and subsequent transformation into a tight binding complex (IR*). In washout experiments, [(3)H] telmisartan dissociated from the receptor with a half-life of 29 min and the Ang II-mediated IP accumulation response was 50% maximally restored within 24 min, whereas values for [(3)H] olmesartan were 72 min and 76 min, respectively. CONCLUSIONS AND IMPLICATIONS: The high degree of insurmountability, slow dissociation, and high affinity of olmesartan for its receptor may relate to its ability to stabilise IR* via the carboxyl group of its imidazole core. In comparison, telmisartan displays a less potent interaction with the receptor.  相似文献   
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HPLC-MS法同时测定人血浆中氯沙坦及其代谢物EXP3174   总被引:1,自引:0,他引:1  
目的:建立人血浆中氯沙坦及其代谢物EXP3174同时测定的HPLC-MS方法,并研究健康受试者单剂量口服氯沙坦钾片后氯沙坦及其代谢物EXP3174的药代动力学特征. 方法:血浆样品以乙腈沉淀蛋白后,进行HPLC-MS分析,色谱柱为Lichrospher C18,流动相为甲醇-20 mmol·L-1醋酸铵水溶液(含0.1 %的甲酸)(60:40,V/V),氯沙坦及其代谢物EXP3174的检测离子均为m/z 207.1,传输区电压为250 V.12名男性健康受试者口服100 mg氯沙坦钾片后,测定血浆中氯沙坦及其代谢物EXP3174的浓度,计算主要药动学参数.结果:在1~2000 ng·mL-1范围内,氯沙坦及其代谢物EXP3174两者峰面积与内标峰面积的比值和浓度的线性关系均良好,批内、批间RSD均小于10%.受试者口服100 mg氯沙坦钾片后,氯沙坦的血药浓度达峰时间为(1.6±1.1)h,达峰浓度为(890.2±476.4)ng·mL-1,消除半衰期为(2.7±1.6)h;EXP3174的血药浓度达峰时间为(2.9±1.0)h,达峰浓度为(1233±611.6)ng·mL-1,消除半衰期为(6.4±1.2)h.结论:本试验通过选择相同的碎片离子作为氯沙坦及其代谢物EXP3174的检测离子,提高了灵敏度和准确度;所建立的HPLC-MS分析方法准确、灵敏、方便,可用于氯沙坦及其代谢物的人体药动学研究.  相似文献   
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EXP631, 4-(3-thienyl)-α,α, 1-trimethyl-4-piperidinemethanol hemi-fumarate salt ( I ), is a centrally acting non-opioid analgesic compound with monoamine uptake blocking properties. EXP631 has analgesic effects in several animal models. It is intended to be used for the treatment of moderate to moderately severe acute and chronic pain. To characterize the disposition of EXP631, the plasma levels of EXP631 were determined in rats and dogs after single intravenous and oral doses. In rats, EXP631 was rapidly absorbed following a single oral solution dose of 5–20 mg kg?1 with maximum plasma levels detected within 1.2 h post dose. The absorption was complete with an oral bioavailability of 92–131%. The pharmacokinetics was dose independent as measured by either Cmax or AUC values. In fasted dogs, EXP631 was absorbed rapidly and well (F = 81%) from an oral solution with the maximum concentration detected at 20 min post dose. In fed dogs, the absorption from capsules was slower (1.38 h) compared to the solution, but the absorption was complete (F = 115%). An N-desmethyl metabolite ( II ) was found in both rat and dog plasma samples. The structure was confirmed by mass spectroscopy, nuclear magnetic resonance spectroscopy and comparative chromatographic retention times. The metabolite is inactive as an analgesic.  相似文献   
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Angiotensin II (Ang II) administered intracerebroventriculary (icv) at a dose that induces drinking behavior in rats significantly increased K+-stimulated release of [3H] noradrenaline (NA) in hypothalamus without affecting basal [3H] NA release. The observed difference between the effects of Ang II on basal and K+-stimulated [3H]NA release may possibly be due to the fact that peptides are released after increased neuronal activity. It can be suggested that Ang II is important primarily in pathological states and that NA plays a substantial role in the brain Ang II-induced drinking response. The imidazolic nonpeptidic compound 2-n-butyl-4-chloro-5-hydroxymethyl-1-{[2-(1H-tetrazol-5-yl)-biphenyl-4-yl]methyl}imidazole potassium salt (DuP 753, losartan), its active metabolite 2-n-butyl-4-chloro-1-{[2-(1H-tetrazol-5-yl)-biphenyl-4-yl]methyl}imidazole-5-carboxylic acid (EXP 3174) and peptide Ang II analogue, sarmesin, antagonized the Ang II-induced effect on [3H]NA release, in spite of the differences in their chemical structures. Thus, the drugs tested inhibited K+-stimulated [3H]NA release in hypothalamus, acting via the angiotensin (AT) 1 receptor subtype. We could not reject the possibility of a non-receptor mechanism of action for DuP 753, EXP 3174 and sarmesin. This research allows us to suggest a neurochemical mechanism for the modulatory role of these drugs on the NA-ergic system. The Ang II receptor antagonists studied may become important therapeutic agents, which act preferentially on pathologically activated systems. These agents may be of use for the prevention of excessive ingestion of water in some neuropsychotic diseases.  相似文献   
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目的:探讨Losartan在体内对肾素-血管紧张素系统的影响以及国人体内losartan代谢过程,为解释其降压机理及临床合理用药提供参考;方法:以健康受试者为研究对象,采用随机、双盲给予药物和安慰剂,观察受试者血压和体内肾素的变化,以及losartan及其代谢产物在体内代谢过程。结果:血压在用药后6h内下降幅度较大,而肾素活性在8h左右升高幅度最大。以及losartan在服药后3h,药物浓度达到高峰,而其代谢产物EXP3174在服药后8h血药浓度达高峰。血浆肾素活性和EXP3174的AUC0-24成正相关。结论:losartan的降低血压与其代谢产物EXP3174作用直接相关,在降压幅度最大时,肾素的活性也达到最高点。这可能与血管紧张素系统的自身调节有关。  相似文献   
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