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1.
目的 研究壳三糖在大鼠体内的组织分布及排泄。方法 建立并验证了大鼠组织、尿液和粪便中壳三糖的高效液相色谱-质谱联用(LC-MS/MS)检测方法。大鼠灌胃给药壳三糖35 mg/kg后,分别在0.5、1.5、3 h 摘取组织,0 h - 4 h、4 h - 8 h、8 h - 12 h、12 h - 24 h 、24 h - 36 h、36 – 48 h时间段收集尿液和粪便。用建立的LC-MS/MS方法测定组织、尿液和粪便中的壳三糖含量。结果 组织、尿液和粪便中壳三糖在10 - 10000 ng/mL的浓度范围内线性良好,日内、日间精密度的相对标准偏差(relative standard deviation,RSD )≤14.20%,准确度的相对误差(relative error,RE)为?11.30%~8.33%,提取回收率为85.2% - 97.9%,没有明显的基质效应,在室温放置24 h、反复冻融以及-40℃放置30天的条件下稳定性良好,满足生物样品的检测需求。灌胃给药后,0.5 h就可以在主要组织检测到壳三糖,1.5 h肾脏中壳三糖含量明显升高,3 h未在大脑中检测到壳三糖。48 h后壳三糖在尿液、粪便中的排泄率分别为7.15%、72.80%。结论 壳三糖主要以原型的形式在大鼠体内分布和排泄,壳三糖在大鼠各组织中的分布较为广泛,以肝和肾为主,粪便是壳三糖的主要排泄途径。  相似文献   
2.
The objective of the present study was the development and validation of the method for determining AMB-FUBINACA and its metabolite - AMB-FUBINACA O-desmethyl acid – in blood samples, followed by verification of the method in toxicological judicial and forensic medicine practice employing the example of post-aggression suicide. Most likely in consequence of development of adverse effects resulting in psychotic symptoms, a male being under the influence of the synthetic cannabinoid AMB-FUBINACA and the new synthetic opioid U-47700, mortally wounded his female partner and subsequently committed suicide. Identification and determination of the afore-mentioned xenobiotics in blood samples collected from the male and female victims were performed employing high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The analytes were isolated from blood samples using the solid phase extraction (SPE) method. The blood samples collected from the male and female demonstrated respectively 110 and 196 ng/mL of AMB-FUBINACA O-desmethyl acid metabolite, 1935 and 357 ng/mL of U-47700, 250 and 200 ng/mL of N-desmethyl-U-47700, as well as 410 and 200 ng/mL of N,N-didesmethyl-U-47700. The concentration values of new psychoactive substances (NPS’s) in blood samples originating from the male and female were within the ranges encountered in cases of poisoning, including these resulting in death. Nevertheless, the evident signs of exsanguination proof that the woman was alive when she sustained lethal injuries. The presented cases illustrate the difficult to be anticipated effect exerted on the users by NPS’s.  相似文献   
3.
The ingestion of the insecticide chlorpyrifos leads to fatal intoxication in suicidal cases, and its distribution can be assessed only after post-mortem. This study attempted to investigate the distribution of chlorpyrifos in forensic visceral tissue samples like stomach, liver, kidney, heart, brain, lung, spleen, muscle and body fluids like blood and urine by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) with the liquid-liquid extraction method. An analysis time of 8.77 min with 1 μl as an injection volume was chosen. The results obtained are analysed using Labsolutions insight LCMS software, considering Multiple Reaction Monitoring (MRM) and Retention Time (RT). Our findings depict that the stomach tissue has very high concentrations of chlorpyrifos, which suggests the possibility of high distribution and aspiration in the stomach tissue. The concentration of chlorpyrifos in stomach tissue ranged from 816 to 901 μg/g in male cadavers and from 443 to 612 μg/g in female cadavers. Among all the tissues, the stomach tissue showed the highest concentration, while the lowest concentration was found in muscle. Metabolic distribution of chlorpyrifos from the stomach contents to the other surrounding organs may occur and hence the concentrations of CPF were also seen in other organs like the liver, lung, kidney, brain, and muscle. These toxicological results from autopsy findings, together with LC-MS/MS indicate that stomach tissue examination gives an accurate profile of insecticide poisoning in forensic samples with acute poisoning.  相似文献   
4.
采用液相色谱-质谱(LC-MS)联用技术研究他克莫司的有关物质。采用Agilent Eclipse Plus-C18(150 mm × 4.6 mm,3.5 μm)色谱柱,以0.01%甲酸水溶液-乙腈-甲基叔丁基醚为流动相体系,对他克莫司及其强制降解试验样品中的有关物质进行梯度洗脱分离;电喷雾正离子化-四极杆-飞行时间串联质谱法(ESI-Q-TOF/MS)测定各有关物质的母离子及碎片离子的准确质荷比和元素组成,并解析鉴定有关物质的结构。在所建立的条件下,他克莫司与其有关物质分离良好,检测并鉴定出35个主要有关物质,其中2个分别为他克莫司的互变异构体Ⅰ和Ⅱ(他克莫司的有效成分),3个为美国药典收载的已知杂质,其余30个为新鉴定的未知有关物质。研究结果可为他克莫司发酵生产过程的质量控制提供参考依据。  相似文献   
5.
Tacrolimus is one of the most commonly used immunosuppressive agents in animal models of transplantation. However, in these models, oral administration is often problematic due to the lowered compliance associated with highly invasive surgery and due to malabsorption in the intestinal tract. Therefore, we carried out a study to determine the pharmacokinetics of tacrolimus after intramuscular (IM) injection and to determine the optimal IM dosing regimens in primate models. Six male cynomolgus monkeys (Macaca fascicularis) were used in the study. Doses of 0.1 mg/kg and 5 mg were administered via IM injection and oral administration, respectively, once to determine single-dose pharmacokinetics and once daily for 5 days to determine multiple-dose pharmacokinetics. According to pharmacokinetic model estimates, the inter- and intra-individual variabilities in bioavailability following IM injection were remarkably reduced compared with those following oral administration. Monte Carlo simulations revealed that Cpeak, Ctrough and AUC would also have less variability following IM injection compared with oral administration. In this study, we found that the pharmacokinetic characteristics of tacrolimus were more constant following IM injection compared with oral administration. These results suggest that IM injection can be an alternative route of administration fin non-human primate model studies.  相似文献   
6.
Daclatasvir hydrochloride (DCV) is the active pharmaceutical ingredient of Daklinza, a marketed product for the treatment of hepatitis C viral infection. The intrinsic stability of daclatasvir was evaluated via a forced degradation study. DCV was found to be stable in the solid state. In solution, its carbamate moiety is susceptible to basic hydrolysis, whereas its imidazole is liable to base-mediated autoxidation to form degradants 1 and 3, 7-8, respectively. The imidazole moiety can also be oxidized to form degradants 6-7 in the presence of hydrogen peroxide or azobisisobutyronitrile. The chloro-adduct degradant 9 was also observed in hydrogen peroxide solution. Furthermore, the imidazole moiety is sensitive to photodegradation in solution. Degradants 2-8 were observed in a solution of DCV exposed to high intensity light/UV light; the formation of degradants 2 and 5-8 was postulated through 4 degradation pathways. The degradants 3 and 4 were deemed to be secondary degradants of 7 and 5, respectively.  相似文献   
7.
目的建立超高效液相色谱串联质谱法(UPLC-MS/MS)同时检测痰液中3种药物异烟肼(isoniazid,INH)、左氧氟沙星(levofloxacin,LFX)和吡嗪酰胺(pyrazinamide,PZA)浓度的方法,冒在为实现临床个体化用药提供帮助。方法痰液样品离心后经甲醇/乙腈蛋白沉淀法预处理后进样液质联用仪进行分析。实验采用的流动相A为含0.1%甲酸的水溶液,流动相B为含0.1%甲酸的乙腈;流速0.35mL·min^-1;采用ACQUITY UPLAC HSS T31.8μm column(2.1mm×100mm,Waters公司)分离;采用电喷零电离源,采用多反应监测(multiple reaction monitoring,MRM)模式对待测物进行正离子扫描检测。此外,本试验盲态收集5例患者的痰液,用该法进行定量分析。结果测得痰液中INH、PZA和LFX分别在48~6000 ng·mL^-1(r=0.9988)、480~60000 ng·mL^-1(r=0.9993)、120~15000 ng·mL^-1(r=0.9995)内表现出良好的线性关系。INH、PZA和LFX 3种药物的日内和日间精密度均低于15%,且3种药物的提取回收率均处于97.21%~107.80%之间。7例受试者体内均检测到药物INH,质量浓度分别为44.74、120.1、301.5、481、595.5、1220及1570 ng·mL^-1;PZA的质量浓度分别为104.2、6273.34和3185 ng·mL^-1;1例受试者检出LFX,质量浓度为199.86 ng·mL^-1。结论本试验建立了痰液中INH、PZA及LFX的检测方法,具有灵敏度高、测定结果准确、快速等诸多优点,可以应用于临床治疗药物的监测。  相似文献   
8.
吴昊  于小红  马光朝  马致洁  章从恩 《中草药》2020,51(21):5501-5508
目的 观察甘草炮制雷公藤Tripterygium wilfordii后对小鼠血清中代谢产物的影响,初步探讨其降低肝毒性的可能代谢通路。方法 将C57BL/6小鼠随机分为对照(Con)组、雷公藤(Raw)组、甘草炮制雷公藤(Pro)组,观察小鼠肝组织病理变化,检测小鼠肝功能生化指标、炎症因子水平;利用液质联用(LC-MS)技术结合代谢组学方法,对各组间的代谢差异进行表征。结果 与Raw组相比,Pro组小鼠肝组织损伤显著改善,肝功能生化指标、炎症因子水平显著降低,表明甘草炮制雷公藤后可以降低小鼠肝毒性;共筛选出脂肪酸、磷脂酸、甘油酯、磷脂酰胆碱、胆酸等12个潜在生物标志物,主要涉及脂肪酸生物合成、甘油磷脂代谢、花生四烯酸代谢等9个代谢通路。结论 甘草炮制雷公藤可有效降低小鼠的肝毒性,其机制可能与调节脂肪酸代谢等通路相关,为其临床合理应用提供参考依据。  相似文献   
9.
A sensitive and rapid liquid chromatography tandem mass spectrometry (LC-MS/MS) method was established for the quantification of total and unbound concentrations of LY3214996, an extracellular signal-regulated kinase inhibitor; abemaciclib, a cyclin-dependent kinase 4/6 inhibitor; and abemaciclib active metabolites, M2 and M20, in human plasma, brain tumor, and cerebrospinal fluid samples. The method was validated over a concentration range of 0.2–500 nM within a total run time of 3.8 min using isocratic elution on a Kinetex™ F5 column. Detection was performed on a Sciex QTRAP 6500+ mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. The intra- and inter-batch accuracy as well as the precision of the method for all matrices was within ±20% and ≤20% at the lower limit of quantification, and within ±15% and ≤15% for other quality control levels for all analytes. The unbound fractions of drugs and metabolites in spiked and patient samples were determined using an optimized equilibrium dialysis. The validated method was successfully applied in a phase 0/2 clinical trial to assess the central nervous system penetration of LY3214996 and abemaciclib.  相似文献   
10.
张宇  秦臻  孙旸  吕加国  吴芳  刘霞 《药学实践杂志》2020,38(3):237-240,249
目的研究HMS-01在大鼠体内的药动学,为后续研究提供支持。方法采用液相色谱-串联质谱(LCMS/MS)技术,建立灵敏、特异的测定血浆等生物样品中HMS-01浓度的分析方法,用建立的方法开展HMS-01在大鼠体内药动学研究。在SD大鼠上分别进行了1个剂量单次灌胃给药、1个剂量单次静注给药的药动学研究,以获得基本药动学参数。结果大鼠静脉注射1 mg/kg的HMS-01后,雄性与雌性大鼠血浆浓度-时间曲线下面积(AUC0-t)分别为221和409 ng·h/ml,平均清除率分别为4.53和2.41 L/h·kg,平均血浆消除半衰期分别为0.786和1.27 h,表观分布容积分别为5.13和3.82 L/kg。灌胃给予30 mg/kg的HMS-01后,在大鼠体内血浆浓度达峰时间tmax为1.17 h,达峰浓度cmax为1243 ng/ml,消除半衰期(t1/2)为2.00 h。雄、雌大鼠AUC0-t分别为2271和8529 ng·h/ml,生物利用度分别为34.3%和69.5%。结论HMS-01在大鼠体内的药动学过程存在显著的性别差异,口服吸收较好,雌性大鼠的生物利用度远高于雄性。  相似文献   
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