全文获取类型
收费全文 | 950篇 |
免费 | 74篇 |
国内免费 | 16篇 |
专业分类
化学 | 783篇 |
力学 | 92篇 |
综合类 | 3篇 |
数学 | 87篇 |
物理学 | 75篇 |
出版年
2024年 | 3篇 |
2023年 | 12篇 |
2022年 | 65篇 |
2021年 | 54篇 |
2020年 | 42篇 |
2019年 | 41篇 |
2018年 | 30篇 |
2017年 | 55篇 |
2016年 | 50篇 |
2015年 | 49篇 |
2014年 | 33篇 |
2013年 | 93篇 |
2012年 | 78篇 |
2011年 | 53篇 |
2010年 | 36篇 |
2009年 | 65篇 |
2008年 | 35篇 |
2007年 | 35篇 |
2006年 | 43篇 |
2005年 | 32篇 |
2004年 | 31篇 |
2003年 | 24篇 |
2002年 | 10篇 |
2001年 | 4篇 |
2000年 | 10篇 |
1999年 | 9篇 |
1998年 | 10篇 |
1997年 | 10篇 |
1996年 | 7篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1993年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 6篇 |
1987年 | 3篇 |
1983年 | 1篇 |
1971年 | 1篇 |
排序方式: 共有1040条查询结果,搜索用时 15 毫秒
11.
变系数计量经济学联立模型的局部线性工具向量估计及其性质 总被引:3,自引:1,他引:2
联立方程计量经济学模型在经济政策制定、经济结构分析和经济预测方面起着重要作用。本文首次提出了我国宏观经济的一类变系数联立模型,并建立了函数系数的局部线性工具向量估计,同时在时间点列固定设计、经济变量随机设计条件下,研究了估计量的大样本性质。与我国宏观经济经典线性联立模型相比,变系数联立模型拟合效果更优。另外它也有助于克服我国宏观经济数据不多而造成的非参数方法应用困难的现实情况。 相似文献
12.
13.
Silvia Migliari Maura Scarlattei Giorgio Baldari Claudia Silva Livia Ruffini 《Molecules (Basel, Switzerland)》2022,27(14)
Background: Nowadays, in Nuclear Medicine, clinically applied radiopharmaceuticals must meet quality release criteria such as high radiochemical purity and radiochemical yield. Many radiopharmaceuticals do not have marketing authorization and have no dedicated monograph within European Pharmacopeia (Ph. Eur.); therefore, general monographs on quality controls (QCs) have to be applied for clinical application. These criteria require standardization and validation in labeling and preparation, including quality controls measurements, according to well defined standard operation procedures. However, QC measurements are often based on detection techniques that are specific to a certain chromatographic system. Several radiosyntheses of [68Ga]Ga-radiopharmaceuticals are more efficient and robust when they are performed with 2-[4-(2-hydroxyethyl)piperazin-1-yl] ethanesulfonic acid (HEPES) buffer, which is considered as an impurity to be assessed in the QC procedure, prior to clinical use. Thus, Ph. Eur. has introduced a thin-layer chromatography (TLC) method to quantify the HEPES amount that is present in [68Ga]Ga-radiopharmaceuticals. However, this is only qualitative and has proven to be unreliable. Here we develop and validate a new high-performance liquid chromatography (UV-Radio-HPLC) method to quantify the residual amount of HEPES in 68Ga-based radiopharmaceuticals. Method: To validate the proposed UV-Radio-HPLC method, a stepwise approach was used, as defined in the guidance document that was adopted by the European Medicines Agency (CMP/ICH/381/95 2014). The assessed parameters are specificity, linearity, precision (repeatability), accuracy, and limit of quantification. A range of concentrations of HEPES (100, 80, 60, 40, 20, 10, 5, 3 μg/mL) were analyzed. Moreover, to test the validity and pertinence of our new HPLC method, we analyzed samples of [68Ga]Ga-DOTATOC; [68Ga]Ga-PSMA; [68Ga]Ga-DOTATATE; [68Ga]Ga-Pentixafor; and [68Ga]Ga-NODAGA-Exendin-4 from different batches that were prepared for clinical use. Results: In the assessed samples, HEPES could not be detected by the TLC method that was described in Ph. Eur. within 4 min incubation in an iodine-saturated chamber. Our developed HPLC method showed excellent linearity between 3 and 100 μg/mL for HEPES, with a correlation coefficient (R2) for calibration curves that was equal to 0.999, coefficients of variation (CV%) < 2%, and percent deviation value of bias from 100% to 5%, in accordance with acceptance criteria. The intra-day and inter-day precision of our method was statistically confirmed and the limit-of-quantification (LOQ) was 3 μg/mL, confirming the high sensitivity of the method. The amount of HEPES that was detected with our developed HPLC method in the tested [68Ga]Ga-radiopharmaceuticals resulted well below the Ph. Eur. limit, especially for [68Ga]Ga-NODAGA-Exendin-4. Conclusions: The TLC method that is described in Ph. Eur. to assess residual HEPES in [68Ga]-based radiopharmaceuticals may not be sufficiently sensitive and thus unsuitable for QC release. Our new HPLC method was sensitive, quantitative, reproducible, and rapid for QCs, allowing us to exactly determine the residual HEPES amount in [68Ga]Ga-radiopharmaceuticals for safe patient administration. 相似文献
14.
15.
Kyeong‐Ryoon Lee Sung Heum Choi Jin‐Sook Song Hyewon Seo Yoon‐Jee Chae Hwang Eui Cho Jin Hee Ahn Sung‐Hoon Ahn Myung Ae Bae 《Biomedical chromatography : BMC》2013,27(7):846-852
In this study, we developed a method for the determination of PF‐04620110 (2‐{(1r,4r)‐4‐[4‐(4‐amino‐5‐oxo‐7,8‐dihydropyrimido[5,4‐f][1,4]oxazepin‐6(5H)‐yl)phenyl]cyclohexyl}acetic acid), a novel diacylglycerol acyltransferase 1 (DGAT‐1) inhibitor, in rat plasma and validated it using liquid chromatography–tandem mass spectrometry (LC‐MS/MS). Rat plasma samples were processed following a protein precipitation method by using acetonitrile and were then injected into an LC‐MS/MS system for quantification. PF‐04620110 and imipramine (internal standard) were separated using a Hypersil Gold C18 column, with a mixture of acetonitrile and 10 mm ammonium formate (90:10, v/v) as the mobile phase. The ion transitions monitored in positive‐ion mode [M + H]+ of multiple‐reaction monitoring were m/z 397.0 → 260.2 for PF‐04620110 and m/z 280.8 → 86.0 for imipramine. The detector response was specific and linear for PF‐04620110 at concentrations within the range 0.05–50 µg/mL and the signal‐to‐noise ratios for the samples were ≥10. The intra‐ and inter‐day precision and accuracy of the method matched the acceptance criteria for assay validation. PF‐04620110 was stable under various processing and/or handling conditions. PF‐04620110 concentrations in the rat plasma samples could be measured up to 24 h after intravenous or oral administration of PF‐04620110, suggesting that the assay is useful for pharmacokinetic studies in rats. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
16.
Ariana Borges Souza Monique Rodrigues Moreira Carly Henrique Gambeta Borges Marília Rodrigues Simão Jairo Kenupp Bastos João Paulo Barreto de Sousa Sérgio Ricardo Ambrosio Rodrigo Cassio Sola Veneziani 《Biomedical chromatography : BMC》2013,27(3):280-283
The Copaifera species (Leguminoseae) are popularly known as ‘copaíba’ or ‘copaíva’ and are grown in the states of Amazonas, Pará and Ceará in northern Brazil. The oleoresins obtained from these species have been extensively used owing to their pharmacological potential and their application in cosmetic and pharmaceutical preparations. In the present study, the development and validation of a novel, rapid and efficient RP‐HPLC methodology for the analysis of the diterpene (?)‐copalic acid (CA), pointed out as the only chemical marker of the Copaifera genus, are described. The regression equation (Y = 26,707x ? 29,498) was obtained with good linearity (r2 = 0.9993) and the limits of quantification and detection were 9.182 and 3.032 µg/mL, respectively. The precision and the accuracy of the method were adequate (lower than 4%). Finally, the validation parameters evaluated were satisfactorily met, so the developed method represents a suitable tool for application in the quality control of such natural products. Further studies aiming to develop analytical methodologies for each Copaifera species using a more representative number of chemical markers should be performed. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
17.
18.
S. Chandrasekaran K. Gopal P. X. Franklin Balasubramanian Jaganatha Sivakumar Gajendra Singh Shridhar Narayanan B. Gopalan Ansar A. Khan 《Biomedical chromatography : BMC》2013,27(8):1018-1026
The present investigation describes the development and validation of a sensitive liquid chromatography–mass spectrometry/mass spectrometry (LC‐MS/MS) method for the estimation of dorsomorphin in rat plasma. A sensitive LC‐MS/MS method was developed using multiple reaction monitoring mode, with the transition of m/z (Q1/Q3) 400.2/289.3 for dorsomorphin and m/z (Q1/Q3) 306.2/236.3 for zaleplon. Chromatographic separation was achieved on a reverse phase Agilent XDB C18 column (100 × 4.6 mm, 5 µm). The mobile phase consisted of acetonitrile and 5 mm ammonium acetate buffer (pH 6.0) 90:10 v/v, at a flow rate of 0.8 mL/min. The effluence was ionized in positive ion mode by electrospray ionization (ESI) and quantitated by mass spectrometry. The retention times of dorsomorphin and internal standard were found to be 2.13 and 1.13 min, respectively. Mean extraction recovery of dorsomorphin and internal standard in rat plasma was above 80%. Dorsomorphin calibration curve in rat plasma was linear (r2 ≥ 0.99) ranging from 0.005 to 10 µg/mL. Inter‐day and intra‐day precision and accuracy were found to be within 85–115% (coefficient of variation). This method was successfully applied for evaluation of the oral pharmacokinetic profile of dorsomorphin in male Wistar rats. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
19.
Venkata Rami Reddy Vaka Jaswanth Kumar Inamadugu Nageswara Rao Pilli Mullangi Ramesh Hussain Reddy Katreddi 《Biomedical chromatography : BMC》2013,27(11):1406-1412
An improved, simple and highly sensitive LC‐MS/MS method has been developed and validated for quantification of febuxostat with 100 μL human plasma using febuxostat‐d7 as an internal standard (IS) according to regulatory guidelines. The analyte and IS were extracted from human plasma via liquid–liquid extraction using diethyl ether. The chromatographic separation was achieved on a Zorbax C18 column using a mixture of acetonitrile and 5 mm ammonium formate (60:40, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The total run time was 5.0 min and the elution of febuxostat and IS occurred at 1.0 and 1.5 min, respectively. A linear response function was established for the range of concentrations 1–6000 ng/mL (r > 0.99). The precursor to product ion transitions monitored for febuxostat and IS were m/z 317.1 → 261.1 and 324.2 → 262.1, respectively. The intra‐ and inter‐day precisions (%RSD) were within 1.29–9.19 and 2.85–7.69%, respectively. The proposed method was successfully applied to pharmacokinetic studies in humans. Copyright © 2013 John Wiley & Sons, Ltd. 相似文献
20.
Determination of mazindol in human oral fluid by high performance liquid chromatography–electrospray ionization mass spectrometry 下载免费PDF全文
Marcella Herbstrith de Oliveira Graciela Carlos Ana Maria Bergold Flavio Pechansky Renata Pereira Limberger Pedro Eduardo Fröehlich 《Biomedical chromatography : BMC》2014,28(8):1064-1069
Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography–mass spectrometry (LC‐MS). The LC system consisted of an LC‐MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2–20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献