全文获取类型
收费全文 | 2666篇 |
免费 | 93篇 |
国内免费 | 19篇 |
专业分类
化学 | 1789篇 |
晶体学 | 20篇 |
力学 | 57篇 |
数学 | 480篇 |
物理学 | 432篇 |
出版年
2023年 | 23篇 |
2022年 | 34篇 |
2021年 | 96篇 |
2020年 | 56篇 |
2019年 | 57篇 |
2018年 | 56篇 |
2017年 | 44篇 |
2016年 | 98篇 |
2015年 | 83篇 |
2014年 | 101篇 |
2013年 | 165篇 |
2012年 | 164篇 |
2011年 | 229篇 |
2010年 | 144篇 |
2009年 | 122篇 |
2008年 | 163篇 |
2007年 | 171篇 |
2006年 | 130篇 |
2005年 | 118篇 |
2004年 | 110篇 |
2003年 | 80篇 |
2002年 | 79篇 |
2001年 | 31篇 |
2000年 | 25篇 |
1999年 | 26篇 |
1998年 | 18篇 |
1997年 | 19篇 |
1996年 | 24篇 |
1995年 | 19篇 |
1994年 | 29篇 |
1993年 | 22篇 |
1992年 | 16篇 |
1991年 | 16篇 |
1990年 | 17篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 10篇 |
1986年 | 12篇 |
1985年 | 13篇 |
1984年 | 15篇 |
1983年 | 16篇 |
1982年 | 22篇 |
1981年 | 14篇 |
1980年 | 4篇 |
1979年 | 6篇 |
1978年 | 14篇 |
1977年 | 4篇 |
1975年 | 6篇 |
1974年 | 5篇 |
1965年 | 3篇 |
排序方式: 共有2778条查询结果,搜索用时 15 毫秒
101.
Simple HPLC‐UV for the quantification of a new leishmanicidal candidate (E)‐1‐4(trifluoromethyl) benzylidene)‐5‐(2‐4‐dichlorozoyl) carbonylhydrazine (LASSBio‐1736) in rat plasma for pharmacokinetics assessment 下载免费PDF全文
Barbra Katyuschya Sanches Moraes Lisiane Bajerski Alcides Parisotto Carlos Eduardo da Rosa Silva Marina Amaral Alves Eliezer de Jesus Barreiro Rodrigo José Freddo Teresa Dalla Costa Lídia Moreira Lima Sandra Elisa Haas 《Biomedical chromatography : BMC》2016,30(7):1029-1035
In this study, a sensitive HPLC‐UV assay was developed and validated for the determination of LASSBio‐1736 in rat plasma with sodium diclofenac as internal standard (IS). Liquid–liquid extraction using acetonitrile was employed to extract LASSBio‐1736 and IS from 100 μL of plasma previously basified with NaOH 0.1 M. Chromatographic separation was carried on Waters Spherisorb®S5 ODS2 C18 column (150 × 4.6 mm, 5 μm) using an isocratic mobile phase composed by water with triethylamine 0.3% (pH 4), methanol and acetonitrile grade (45:15:40, v/v/v) at a flow rate of 1 mL/min. Both LASSBio‐1736 and IS were eluted at 4.2 and 5 min, respectively, with a total run time of 8 min only. The lower limit of quantification was 0.2 μg/mL and linearity between 0.2 and 4 μg/mL was obtained, with an R2 > 0.99. The accuracy of the method was >90.5%. The relative standard deviations intra and interday were <6.19 and <7.83%, respectively. The method showed the sensitivity, linearity, precision, accuracy and selectivity required to quantify LASSBio‐1736 in preclinical pharmacokinetic studies according to the criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献
102.
Juan Luis Vázquez Ivan Velazco-Cabral Dr. Marcos Flores-Álamo Gleb Turlakov Geraldina Rodríguez Dr. Ivana Moggio Dr. Eduardo Arias Dr. Eduardo Peña-Cabrera Dr. Miguel A. Vázquez 《Chemistry (Weinheim an der Bergstrasse, Germany)》2022,28(71):e202202446
A series of new symmetrical highly substituted BODIPYs 6 a – l was synthesized through a prefunctionalization approach in 35 %–89 % yields from the pyrrole core. This strategy allowed modulation of the substituents at the different positions based on the choice of Fischer's alkynyl carbenes, oxazolones and aldehydes used as precursors. The substituent variation at positions 2, 6, 3 and 5 had the greatest effect on the modulation of their photophysical properties such as absorption (λabs) and emission (λem) wavelengths, extinction coefficient (ϵ), quantum yields (ϕ), Stokes shifts (Δν), fluorescence decay, radiative (krad) and non-radiative (knr) constants and the CIE 1931 coordinates. Theoretical calculations allowed to corroborate the effect of the substituents of meso-position on the modification of the dihedral angles. Cyclic voltammetry studies revealed that the BODIPY series presents similar redox potential behavior, being electrochemically active even in successive cycles, which suggests that transport by diffusion is the dominant process. 相似文献
103.
Jadriane A. Xavier Thaissa L. Silva Eduardo Caio Torres-Santos Camila Calado de Vasconcelos Anastacio Boane Ricardo Alexandre dos Santos Andre Felippe A. Xavier Marília O.F. Goulart 《Current Opinion in Electrochemistry》2021
This review discusses the state of the art, challenges, and perspectives in recent applications of nitroaromatics and nitroheteroaromatics, which are redox-bio-activated drugs or leads, in Medicinal Chemistry. It deals mainly with the electrochemical approach toward the electron transfer-based molecular mechanisms of drug action, drug design, estimation and measurement of redox potentials, correlation of physicochemical and pharmacological data, and electrochemical studies of the main representatives of nitro-containing prodrugs, along with approaches to combat their toxicity issues, aiming at a better therapeutic profile. Electrochemical investigation plays essential roles, being strategic in the design and discovery of potential medicines. 相似文献
104.
Dr. Stefano Elli Dr. Eduardo Stancanelli Dr. Zhangjie Wang Dr. Maurice Petitou Prof. Jian Liu Dr. Marco Guerrini 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(51):11814-11818
Heparin binds to and activates antithrombin (AT) through a specific pentasaccharide sequence, in which a trisaccharide subsite, containing glucuronic acid (GlcA), has been considered as the initiator in the recognition of the polysaccharide by the protein. Recently it was suggested that sulfated iduronic acid (IdoA2S) could replace this “canonical” GlcA. Indeed, a heparin octasaccharidic sequence obtained by chemoenzymatic synthesis, in which GlcA is replaced with IdoA2S, has been found to similarly bind to and activate antithrombin. By using saturation-transfer-difference (STD) NMR, NOEs, transferred NOEs (tr-NOEs) NMR and molecular dynamics, we show that, upon binding to AT, this IdoA2S unit develops comparable interactions with AT as GlcA. Interestingly, two IdoA2S units, both present in a 1C4-2S0 equilibrium in the unbound saccharide, shift to full 2S0 and full 1C4 upon binding to antithrombin, providing the best illustration of the critical role of iduronic acid conformational flexibility in biological systems. 相似文献
105.
Mireia Casasampere Eduardo Izquierdo Josefina Casas Jos Luís Abad Xiao Liu Ruijuan Xu Cungui Mao Young-Tae Chang Antonio Delgado Gemma Fabrias 《Chemical science》2020,11(48):13044
The use of intact cells in medical research offers a number of advantages over employing cell-free systems. In diagnostics, cells isolated from liquid biopsies can be directly used, speeding up the time of analysis and diminishing the risk of protein degradation by sample manipulation. In drug discovery, studies in live cells take into account aspects neglected in cell-free systems, such as uptake, metabolization, and subcellular concentration by compartmentalization of potential drug candidates. Therefore, probes for studies in cellulo are of paramount importance. Acid ceramidase (AC) is a lysosomal enzyme that hydrolyses ceramides into sphingoid bases and fatty acids. The essential role of this enzyme in the outburst and progress of several diseases, some of them still incurable, is well sustained. Despite the great clinical relevance of AC as a biomarker and therapeutic target, the specific monitoring of AC activity in live cells has remained elusive due to the concomitant existence of neutral and alkaline ceramidases. In this work, we report that 1-deoxydihydroceramides are exclusively hydrolysed by AC. Using N-octanoyl-18-azidodeoxysphinganine as a probe and a BODIPY-substituted bicyclononyne, we show the click-reliant predominant staining of lysosomes, with extra-lysosomal labeling also occurring in some cells. Importantly, using pharmacological and genetic tools together with high resolution mass spectrometry, we demonstrate that both lysosomal and extra-lysosomal staining are AC-dependent. These findings are translated into the specific flow cytometry monitoring of AC activity in intact cells, which fills an important gap in the field of diseases linked to altered AC activity.The use of intact cells in medical research offers a number of advantages over employing cell-free systems. 相似文献
106.
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
107.
108.
109.
110.