全文获取类型
收费全文 | 680篇 |
免费 | 22篇 |
国内免费 | 2篇 |
专业分类
化学 | 475篇 |
晶体学 | 3篇 |
力学 | 13篇 |
数学 | 92篇 |
物理学 | 121篇 |
出版年
2023年 | 8篇 |
2022年 | 9篇 |
2021年 | 15篇 |
2020年 | 19篇 |
2019年 | 13篇 |
2018年 | 14篇 |
2017年 | 16篇 |
2016年 | 25篇 |
2015年 | 26篇 |
2014年 | 23篇 |
2013年 | 45篇 |
2012年 | 46篇 |
2011年 | 56篇 |
2010年 | 27篇 |
2009年 | 30篇 |
2008年 | 34篇 |
2007年 | 26篇 |
2006年 | 36篇 |
2005年 | 47篇 |
2004年 | 30篇 |
2003年 | 18篇 |
2002年 | 25篇 |
2001年 | 15篇 |
2000年 | 7篇 |
1999年 | 6篇 |
1998年 | 7篇 |
1997年 | 6篇 |
1996年 | 7篇 |
1995年 | 5篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 8篇 |
1987年 | 3篇 |
1984年 | 4篇 |
1982年 | 3篇 |
1981年 | 2篇 |
1980年 | 2篇 |
1979年 | 2篇 |
1977年 | 3篇 |
1976年 | 5篇 |
1975年 | 4篇 |
1974年 | 2篇 |
1972年 | 1篇 |
1966年 | 2篇 |
1963年 | 2篇 |
1958年 | 2篇 |
1874年 | 1篇 |
排序方式: 共有704条查询结果,搜索用时 15 毫秒
81.
Lone AM Bachovchin DA Westwood DB Speers AE Spicer TP Fernandez-Vega V Chase P Hodder PS Rosen H Cravatt BF Saghatelian A 《Journal of the American Chemical Society》2011,133(30):11665-11674
Peptidases play vital roles in physiology through the biosynthesis, degradation, and regulation of peptides. Prolyl endopeptidase-like (PREPL) is a newly described member of the prolyl peptidase family, with significant homology to mammalian prolyl endopeptidase and the bacterial peptidase oligopeptidase B. The biochemistry and biology of PREPL are of fundamental interest due to this enzyme's homology to the biomedically important prolyl peptidases and its localization in the central nervous system. Furthermore, genetic studies of patients suffering from hypotonia-cystinuria syndrome (HCS) have revealed a deletion of a portion of the genome that includes the PREPL gene. HCS symptoms thought to be caused by lack of PREPL include neuromuscular and mild cognitive deficits. A number of complementary approaches, ranging from biochemistry to genetics, will be required to understand the biochemical, cellular, physiological, and pathological mechanisms regulated by PREPL. We are particularly interested in investigating physiological substrates and pathways controlled by PREPL. Here, we use a fluorescence polarization activity-based protein profiling (fluopol-ABPP) assay to discover selective small-molecule inhibitors of PREPL. Fluopol-ABPP is a substrate-free approach that is ideally suited for studying serine hydrolases for which no substrates are known, such as PREPL. After screening over 300,000 compounds using fluopol-ABPP, we employed a number of secondary assays to confirm assay hits and characterize a group of 3-oxo-1-phenyl-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile and 1-alkyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile PREPL inhibitors that are able to block PREPL activity in cells. Moreover, when administered to mice, 1-isobutyl-3-oxo-3,5,6,7-tetrahydro-2H-cyclopenta[c]pyridine-4-carbonitrile distributes to the brain, indicating that it may be useful for in vivo studies. The application of fluopol-ABPP has led to the first reported PREPL inhibitors, and these inhibitors will be of great value in studying the biochemistry of PREPL and in eventually understanding the link between PREPL and HCS. 相似文献
82.
Uchiyama K Kondo M Yokochi R Takeuchi Y Yamamoto A Inoue Y 《Journal of separation science》2011,34(13):1525-1530
A simple, selective and rapid analytical method for determination of trimethoprim (TMP) in honey samples was developed and validated. This method is based on a SPE technique followed by HPLC with photodiode array detection. After dilution and filtration, aliquots of 500 μL honey samples were directly injected to an on-line SPE HPLC system. TMP was extracted on an RP SPE column, and separated on a hydrophilic interaction chromatography column during HPLC analysis. At the first detection step, the noise level of the photodiode array data was reduced with two-dimensional equalizer filtering, and then the smoothed data were subjected to derivative spectrum chromatography. On the second-derivative chromatogram at 254 nm, the limit of detection and the limit of quantification of TMP in a honey sample were 5 and 10 ng/g, respectively. The proposed method showed high accuracy (60-103%) with adequate sensitivity for TMP monitoring in honey samples. 相似文献
83.
84.
An application of coupled column ion chromatography (IC)-inductively coupled plasma mass spectrometry (ICP-MS) is presented for speciation of chromium in waste waters. By coupling an anion column with a cation column, both the cationic Cr(III) and anionic Cr(VI) species can be analyzed with detection limits below 0.5 μg/1. The separation of the interfering ions (chloride, chlorate, perchlorate, sulphate, sulphite, sulphide, thiosulphate, carbonate, cyanide and some organic compounds) from the chromium peaks is discussed, and the use of different chromium isotopes for data acquisition is compared. Based on the results, m/z 52 was considered as an ideal isotope for speciation of chromium in waste waters by the coupled column IC-ICP-MS, because it did not suffer from polyatomic interferences and due to the high sensitivity for chromium. The analysis of the waste water samples should be performed as soon as possible after sampling according to the stability tests of the species. 相似文献
85.
Charles E. McKenna Boris A. Kashemirov Mari Fujimolo 《Phosphorus, sulfur, and silicon and the related elements》2013,188(1-4)
Abstract Individual E/Z isomers of the C-methyl ester 1 of α-(hydroxyimino)phosphonoacetic acid (“troika acid”) were recently prepared as dicyclohexylammonium salts and found to be stable at neutral pH.1 On alkaline demethylation followed by pH adjustment to 6–7, E?1 and Z?1 stereospecifically undergo P-Cαand Cα-Cβ cleavage, respectively.1 Herein we report synthesis of the corresponding P-methyl ester from trimethyl phos-phonoacetate 2. The product was isolated as its bis-DCHA+ salt E-3, with stereochemistry assigned by NMR.2 相似文献
86.
Haruhiko Fuwa Prof. Dr. Asami Saito Shinya Naito Keiichi Konoki Prof. Dr. Mari Yotsu‐Yamashita Prof. Dr. Makoto Sasaki Prof. Dr. 《Chemistry (Weinheim an der Bergstrasse, Germany)》2009,15(46):12807-12818
The stereocontrolled total synthesis of the originally proposed ( 1 ) and correct ( 2 ) structures of (+)‐neopeltolide, a novel marine macrolide natural product with highly potent antiproliferative activity against several cancer cell lines as well as potent antifungal activity, has been achieved by exploiting a newly developed Suzuki–Miyaura coupling/ring‐closing metathesis strategy. Alkylborate 44 , which was generated in situ from iodide 34 , was coupled with enol phosphate 8 by a Suzuki–Miyaura coupling. Ring‐closing metathesis of the derived diene 45 followed by stereoselective hydrogenation afforded tetrahydropyran 47 as a single stereoisomer in high overall yield from 34 . Our convergent strategy enabled us to construct the 14‐membered macrolactone core structure of 2 in a rapid and efficient manner. Total synthesis and biological evaluation of synthetic intermediates and designed synthetic analogues, performed to establish the structure–activity relationships of 2 , led to the discovery of a structurally simple yet potent cytotoxic analogue, 9‐demethylneopeltolide ( 54 ). 相似文献
87.
88.
Beverina L Crippa M Landenna M Ruffo R Salice P Silvestri F Versari S Villa A Ciaffoni L Collini E Ferrante C Bradamante S Mari CM Bozio R Pagani GA 《Journal of the American Chemical Society》2008,130(6):1894-1902
Singlet oxygen sensitization by organic molecules is a topic of major interest in the development of both efficient photodynamic therapy (PDT) and aerobic oxidations under complete green chemistry conditions. We report on the design, synthesis, biology, and complete spectroscopic characterization (vis-NIR linear and two-photon absorption spectroscopy, singlet oxygen generation efficiencies for both one- and two-photon excitation, electrochemistry, intrinsic dark toxicity, cellular uptake, and subcellular localization) of three classes of innovative singlet oxygen sensitizers pertaining to the family of symmetric squaraine derivatives originating from pi-excessive heterocycles. The main advantage of pi-extended squaraine photosensitizers over the large number of other known photosensitizers is their exceedingly strong two-photon absorption enabling, together with sizable singlet oxygen sensitization capabilities, for their use at the clinical application relevant wavelength of 806 nm. We finally show encouraging results about the dark toxicity and cellular uptake capabilities of water-soluble squaraine photosensitizers, opening the way for clinical small animal PDT trials. 相似文献
89.
C. M. Mari 《Ionics》2003,9(5-6):365-369
Aim of the lecture is to present the operating principles of non-Nernstian electrochemical devices, the state of the art as
well as the weight of the electrode materials electrocatalytic properties in the design of planar sensors.
Paper presented at the 9th EuroConference on Ionics, Ixia, Rhodes, Greece, Sept. 15–21, 2002. 相似文献
90.
Laura L. Tomasevich Stephen M. Zitelli Chelsey R. Gillen Neal J. Baker Jason M. Conley Mari Lynne Starr Patrick J. Carroll 《Tetrahedron letters》2007,48(4):599-602
Condensation of ninhydrin with tryptamide or tryptamine followed by Lewis acid-induced rearrangement provided yohimbanones that were readily converted to β-carbolines via oxidative ring cleavage. The analogous condensation-rearrangement with 3,4-dimethoxyphenethylamine and ninhydrin afforded an oxyprotoberberine, which was further oxygenated at the 13a position. 相似文献