全文获取类型
收费全文 | 884篇 |
免费 | 206篇 |
国内免费 | 6篇 |
专业分类
化学 | 1083篇 |
力学 | 1篇 |
综合类 | 3篇 |
数学 | 8篇 |
物理学 | 1篇 |
出版年
2024年 | 5篇 |
2023年 | 13篇 |
2022年 | 82篇 |
2021年 | 36篇 |
2020年 | 83篇 |
2019年 | 90篇 |
2018年 | 71篇 |
2017年 | 72篇 |
2016年 | 58篇 |
2015年 | 73篇 |
2014年 | 57篇 |
2013年 | 83篇 |
2012年 | 72篇 |
2011年 | 48篇 |
2010年 | 43篇 |
2009年 | 41篇 |
2008年 | 52篇 |
2007年 | 40篇 |
2006年 | 25篇 |
2005年 | 18篇 |
2004年 | 9篇 |
2003年 | 10篇 |
2002年 | 6篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1997年 | 1篇 |
1996年 | 3篇 |
1994年 | 2篇 |
排序方式: 共有1096条查询结果,搜索用时 15 毫秒
121.
Shouhong Gao Qin Zhan Jingxian Li Qi Yang Xia Li Wansheng Chen Lianna Sun 《Biomedical chromatography : BMC》2010,24(5):472-478
A simple, rapid and sensitive liquid chromatography–tandem mass spectroscopy (LC–MS/MS) method was developed and validated for the determination of ethyl gallate, a pharmacologically active constituent isolated from Lagerstroemia speciosa (Linn.) Pers. This method was used to examine the pharmacokinetics of ethyl gallate and its major metabolite gallic acid in rat plasma using propyl gallate as an internal standard. After precipitation of the plasma proteins with acetonitrile, the analytes were separated on a Zorbax SB‐C18 column (3.5 μm, 2.1 × 50 mm) with an isocratic mobile phase consisted of methanol–acetonitrile–10 mM ammonium acetate (10 : 25 : 65, v/v/v) containing 0.1% formic acid at a flow rate of 0.25 mL/min. The Agilent G6410A triple quadrupole LC/MS system was operated under the multiple‐reaction monitoring mode using the electrospray ionization technique in negative mode. The lower limits of quantification of gallic acid and ethyl gallate of the method were 0.5 and 1.0 ng/mL. The intra‐day and inter‐day accuracy and precision of the assay were less than 8.0%. This method has been applied successfully to a pharmacokinetic study involving the intragastric administration of ethyl gallate to rats. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
122.
Amal Kaddoumi Mitsuhiro Wada Kenichiro Nakashima 《Biomedical chromatography : BMC》2011,25(5):579-587
N‐Nitrosofenfluramine (N‐Fen), a synthetic adulterant in Chinese herbal diet products, is believed to cause hepatotoxicity in people who use these products. N‐Fen is a relatively new compound, and thus pharmacological and toxicological studies are insufficient. The aim of this work was to (1) define N‐Fen's plasma pharmacokinetics and tissue distribution after single intraperitoneal (i.p.) administration of 25 mg/kg to rats; (2) define its bioavailability; and (3) identify fenfluramine (Fen) and norfenfluramine (Norf) as N‐Fen metabolites. N‐Fen rapidly appeared in the circulation and was distributed to all tissues. Norf was found to be the primary metabolite and not Fen. Plasma and tissue levels of N‐Fen and Norf were low with bioavailability of N‐Fen after i.p. administration was <3%. The AUC0−t of N‐Fen in the liver and kidney were 6.6 and 12.1 times, respectively, greater than the brain, and 17.8 and 32.6 times, respectively, greater than the plasma. In conclusion, N‐Fen did not show local accumulation in the liver, the site of toxicity, with concentrations represented as percentage of the total dose ranginng from 0.008 to 0.122%; hence the cause of hepatotoxicity could be related to the mechanisms other than toxicity consequences accumulation. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
123.
Jung‐Woo Bae Chang‐Ik Choi Choon‐Gon Jang Seok‐Yong Lee 《Biomedical chromatography : BMC》2011,25(11):1181-1188
A simple and sensitive liquid chromatography–electrospray ionization–tandem mass spectrometry (LC‐ESI‐MS/MS) technique was developed and validated for the determination of sibutramine and its N‐desmethyl metabolites (M1 and M2) in human plasma. After extraction with methyl t‐butyl ether, chromatographic separation of analytes in human plasma was performed using a reverse‐phase Luna C18 column with a mobile phase of acetonitrile–10 mm ammonium formate buffer (50:50, v/v) and quantified by ESI‐MS/MS detection in positive ion mode. The flow rate of the mobile phase was 200 μL/min and the retention times of sibutramine, M1, M2 and internal standard (chlorpheniramine) were 1.5, 1.4, 1.3 and 0.9 min, respectively. The calibration curves were linear over the range 0.05–20 ng/mL, for sibutramine, M1 and M2. The lower limit of quantification was 0.05 ng/mL using 500 μL of human plasma. The mean accuracy and the precision in the intra‐ and inter‐day validation for sibutramine, M1 and M2 were acceptable. This LC‐MS/MS method showed improved sensitivity and a short run time for the quantification of sibutramine and its two active metabolites in plasma. The validated method was successfully applied to a pharmacokinetic study in human. Copyright © 2011 John Wiley & Sons, Ltd. 相似文献
124.
《Biomedical chromatography : BMC》2018,32(7)
A selective and sensitive liquid chromatography–tandem mass spectrometry method was developed and validated for investigating the pharmacokinetics of umbelliferone, apigenin, genkwanin and hydroxygenkwanin after oral administration of Daphne genkwa extract. Plasma samples were treated by protein precipitation with acetonitrile. Analytes were detected by triple‐quadrupole MS/MS with an ESI source in negative selection reaction monitoring mode. The transitions of m/z 161 → 133 for umbelliferone, m/z 269 → 117 for apigenin, m/z 283 → 268 for genkwanin and m/z 299 → 284 for hydroxygenkwanin were confirmed for quantification. Chromatographic separation was conducted using an Eclipse XDB‐C18 column, and the applied isocratic elution program allowed for simultaneous determination of the four analytes for a total run time of 2.5 min. The linearity was validated over the plasma concentration ranges of 1.421–1421 ng/mL for umbelliferone, 0.845–845 ng/mL for apigenin, 1.025–1025 ng/mL for genkwanin and 0.845–845 ng/mL for hydroxygenkwanin. The extraction recovery rate was >82.7% for each analyte. No apparent matrix effect was observed during the bioanalysis. After full validation, the proposed method was successfully applied to compare the pharmacokinetics of these analytes between normal and arthritic rats. 相似文献
125.
The comparative pharmacokinetics of four bioactive ingredients after administration of Ramulus Cinnamomi–Radix Glycyrrhizae herb pair extract,Ramulus Cinnamomi extract and Radix Glycyrrhizae extract 下载免费PDF全文
Shengnan Wang Lijiao Sun Liqiang Gu Yuanyuan Zhang Simin Zhao Long‐shan Zhao Kai‐shun Bi Xiaohui Chen 《Biomedical chromatography : BMC》2016,30(8):1270-1277
Ramulus Cinnamomi (RC)–Radix Glycyrrhizae (RG) is a classic herb pair, which is commonly used as a fixed form to treat cardiovascular disease in the clinic. Our work aimed to compare the pharmacokinetic difference of cinnamic acid, liquiritin, isoliquiritigenin and glycyrrhetinic acid in rats after oral administration of the RC–RG herb pair extracts [Guizhigancao Decoction (GGD) and Lingguizhugan Decoction (LGZGD)] and the single RC or RG extract. A HPLC‐MS method was developed and validated to study comparative pharmacokinetics. The pharmacokinetic parameters (Cmax, AUC, MRT) of four compounds between the RC–RG herb pair group and the single herb (RC or RG) group showed significant differences (p < 0.05). Compared with the single herb (RC or RG) group, higher peak concentration, slower elimination and larger exposure could be observed after giving the RC–RG herb‐pair extracts. The pharmacokinetic differences might indicate the relativity of remedy in the RC–RG herb pair and provide scientific information for rational administration of the drug in the clinic. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
126.
P. S. Suresh Sanjeev Giri Raghib Husain Ramesh Mullangi 《Biomedical chromatography : BMC》2010,24(10):1052-1058
A highly sensitive, rapid assay method has been developed and validated for the estimation of S‐citalopram (S‐CPM) in rat plasma with liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The assay procedure involves a simple liquid–liquid extraction of S‐CPM and phenacetin (internal standard, IS) from rat plasma with t‐butyl methyl ether. Chromatographic separation was operated with 0.2% formic acid:acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on a Symmetry Shield RP18 column with a total run time of 3.0 min. The MS/MS ion transitions monitored were 325.26 → 109.10 for S‐CPM and 180.10 → 110.10 for IS. Method validation and pre‐clinical sample analysis were performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.5 ng/mL and the linearity was observed from 0.5 to 5000 ng/mL. The intra‐ and inter‐day precisions were in the range of 1.14–5.56 and 0.25–12.3%, respectively. This novel method has been applied to a pharmacokinetic study and to estimate brain‐to‐plasma ratio of S‐CPM in rats. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
127.
Clinical microdialysis (MD) is a minimally invasive sampling technique that offers selective in-vivo measurement of free, active drug or biomolecule concentrations in human tissues and organs. From a regulatory perspective, MD can thus be seen as a suitable scientific tool that meets regulatory requirements for the study of tissue distribution or bioequivalence during drug development. From a clinical perspective, the use of MD in different applications has shown the potential to rationalize drug-dosing regimens and to influence clinical decision-making, although validation and correlation of MD-derived results with clinical response are required to promote routine clinical use of the technique. From an analytical perspective, highly sensitive analytical systems have increasingly become available for MD-sample analysis, and these have further improved the quality and the power of MD-derived information. Given the constant development in recent years, MD data might become an important part of new drug submissions and clinical treatment algorithms, and might positively influence patient benefit in the future. 相似文献
128.
Taiming Liu Zhuo Chen Yuyi Guo Xuehua Jiang Guo Ma 《Biomedical chromatography : BMC》2009,23(7):754-758
A simple, specific and sensitive HPLC method with UV detection was developed and validated for the determination of tectoridin in rat plasma for the first time. Chromatographic separation was performed on a WelchromTM C18 column (150 × 4.6 mm, i.d., 5 µm) at a flow rate of 1.0 mL min?1, using a mixture of methanol–2% HAc aqueous solution (31:69, v/v) as the mobile phase with UV detection at 266 nm. The calibration curves for tectoridin were linear over the concentration range of 1.10–274.40 µg mL?1 in rat plasma. The intra‐ and inter‐day accuracies (RE) were within ?3.23% and 4.11%. The intra‐ and inter‐day precisions (RSD) were not more than 2.74 and 4.72%, respectively. The present method was successfully applied to the pharmacokinetic studies of tectoridin in rats after intravenous administration of three different doses. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
129.
王芷 《广东微量元素科学》2017,24(3)
目的研究去甲万古霉素群体药代动力学指标差异,对患者进行药效学优化。方法选取2015年1月至2015年12月268例感染患者,将其按照年龄分为中青年组和老年组,每组各134例,采用群体药代动力学和药效学优化公式进行计算,分析患者上述指标差异。结果青年组与老年组的群体药代动力学各项指标差异明显具有统计学意义(P0.05)。结论感染患者通过去甲万古霉素药物治疗疗效确切,对革兰阳性菌的杀灭作用明显,采用群体药代动力学和药效学研究后发现,AUC24/MIC能够作为去甲万古霉素的应用指标,并以此指导临床用药效果显著,值得临床应用推广。 相似文献
130.
Moxifloxacin is a representative of the fourth generation of fluoroquinolones. It possesses bacteriostatic activity against Gram-positive and Gram-negative bacteria. A simple and fast high performance liquid chromatography-ultraviolet detection (HPLC-UV) method was developed for moxifloxacin analysis. The separation was performed on C18 column. The mobile phase was a mixture of acetonitrile and 0.4% triethylamine solution. The regression curve was linear over the range 0.2–10.0?µg/mL. The validation parameters obey the European Medicine Agency limits. The in vivo study confirmed the practical application of the method. 相似文献