全文获取类型
收费全文 | 1001篇 |
免费 | 180篇 |
国内免费 | 66篇 |
专业分类
化学 | 973篇 |
力学 | 1篇 |
综合类 | 7篇 |
数学 | 178篇 |
物理学 | 88篇 |
出版年
2024年 | 2篇 |
2023年 | 10篇 |
2022年 | 25篇 |
2021年 | 48篇 |
2020年 | 88篇 |
2019年 | 45篇 |
2018年 | 46篇 |
2017年 | 35篇 |
2016年 | 67篇 |
2015年 | 71篇 |
2014年 | 73篇 |
2013年 | 79篇 |
2012年 | 83篇 |
2011年 | 68篇 |
2010年 | 70篇 |
2009年 | 69篇 |
2008年 | 62篇 |
2007年 | 53篇 |
2006年 | 45篇 |
2005年 | 41篇 |
2004年 | 38篇 |
2003年 | 29篇 |
2002年 | 22篇 |
2001年 | 9篇 |
2000年 | 11篇 |
1999年 | 8篇 |
1998年 | 15篇 |
1997年 | 9篇 |
1996年 | 2篇 |
1995年 | 9篇 |
1994年 | 2篇 |
1993年 | 3篇 |
1992年 | 1篇 |
1991年 | 3篇 |
1989年 | 4篇 |
1987年 | 1篇 |
1981年 | 1篇 |
排序方式: 共有1247条查询结果,搜索用时 15 毫秒
21.
Vinh X. Truong Kun Zhou George P. Simon John S. Forsythe 《Macromolecular rapid communications》2015,36(19):1729-1734
This communication describes the first application of cycloaddition between an in situ generated nitrile oxide with norbornene leading to a polymer crosslinking reaction for the preparation of poly(ethylene glycol) hydrogels under physiological conditions. Hydrogels with high water content and robust physical strength are readily formed within 2–5 min by a simple two‐solution mixing method which allows 3D encapsulation of neuronal cells. This bioorthogonal crosslinking reaction provides a simple yet highly effective method for preparation of hydrogels to be used in bioengineering.
22.
Kuan-Yu Lin Chak Hin Lam Xin-Hui Lin Jung-I Hsu Syuan-Yun Fan Dr. Nitesh K. Gupta Yu-Chun Lin Boon Khoon Tee Jui-Ping Li Dr. Jen-Kun Chen Prof. Dr. Kui-Thong Tan 《化学:亚洲杂志》2021,16(8):937-948
To date, various affinity-based protein labeling probes have been developed and applied in biological research to modify endogenous proteins in cell lysates and on the cell surface. However, the reactive groups on the labeling probes are also the cause of probe instability and nonselective labeling in a more complex environment, e. g., intracellular and in vivo. Here, we show that labeling probes composed of a sterically stabilized difluorophenyl pivalate can achieve efficient and selective labeling of endogenous proteins on the cell surface, inside living cells and in vivo. As compared with the existing protein labeling probes, probes with the difluorophenyl pivalate exhibit several advantages, including long-term stability in stock solutions, resistance to enzymatic hydrolysis and can be customized easily with diverse fluorophores and protein ligands. With this probe design, endogenous hypoxia biomarker in living cells and nude mice were successfully labeled and validated by in vivo, ex vivo, and immunohistochemistry imaging. 相似文献
23.
Dr. Maria S. Ledovskaya Dr. Mikhail V. Polynski Prof. Dr. Valentine P. Ananikov 《化学:亚洲杂志》2021,16(16):2286-2297
Acetylene surrogates are efficient tools in modern organic chemistry with largely unexplored potential in the construction of heterocyclic cores. Two novel synthetic paths to 3,6-disubstituted pyridazines were proposed using readily available acetylene surrogates through flexible C2 unit installation procedures in a common reaction space mode (one-pot) and distributed reaction space mode (two-chamber): (1) an interaction of 1,2,4,5-tetrazine and its acceptor-functionalized derivatives with a CaC2−H2O mixture performed in a two-chamber reactor led to the corresponding pyridazines in quantitative yields; (2) [4+2] cycloaddition of 1,2,4,5-tetrazines to benzyl vinyl ether can be considered a universal synthetic path to a wide range of pyridazines. Replacing water with D2O and vinyl ether with its trideuterated analog in the developed procedures, a range of 4,5-dideuteropyridazines of 95–99% deuteration degree was synthesized for the first time. Quantum chemical modeling allowed to quantify the substituent effect in both synthetic pathways. 相似文献
24.
The demand for more efficient methods of establishing the undetermined stereochemistries of peptidic natural products continues unabated. A new method for microscale stereochemical determination was devised by integrating solid-phase synthesis, split-and-mix randomization, 18O/16O-encoding of d /l -configurations, tandem mass spectrometry, and biological evaluation. Here we applied gramicidin A as the molecule for a blind test. Gramicidin A and its 31 diastereomers were randomly prepared in microgram scale with 18O/16O-stereochemical encoding and subjected to MS/MS-structural determination and cytotoxicity assay. Only the parent gramicidin A was selected from among the 32 stereoisomers, validating the high reliability of the present strategy. 相似文献
25.
Lucia De Rosa Rossella Di Stasi Alessandra Romanelli Luca Domenico DAndrea 《Molecules (Basel, Switzerland)》2021,26(12)
Although a plethora of chemistries have been developed to selectively decorate protein molecules, novel strategies continue to be reported with the final aim of improving selectivity and mildness of the reaction conditions, preserve protein integrity, and fulfill all the increasing requirements of the modern applications of protein conjugates. The targeting of the protein N-terminal alpha-amine group appears a convenient solution to the issue, emerging as a useful and unique reactive site universally present in each protein molecule. Herein, we provide an updated overview of the methodologies developed until today to afford the selective modification of proteins through the targeting of the N-terminal alpha-amine. Chemical and enzymatic strategies enabling the selective labeling of the protein N-terminal alpha-amine group are described. 相似文献
26.
27.
Zhen Wang Ziyang Li Tian Su Xiao Han Zhanwu Hou Yupeng Zheng Jiachen Liu Jun Xu Jeffy Yang Huadong Liu 《Electrophoresis》2021,42(6):793-799
Western blot (protein immunoblot) is a widely used analytical technique in molecular biology. Utilizing the specific recognizing primary antibody, proteins immobilized on various matrix are investigated by subsequent visualization steps, for example, by the horse radish peroxidase conjugated secondary antibody incubation. Methods to improve the sensitivity in protein identification or quantification are appreciated by biochemists. Herein, we report a new strategy to amplify Western blot signals by constructing a probe with proximal labeling and IgG targeting abilities. The R118G mutation attenuated the biotin-AMP binding affinity of the bacterial biotin ligase BirA*, offering a proximity-dependent labeling ability, which could be used as a signal amplifier. We built a BirA*-protein A fusion protein (BioEnhancer) that specifically binds to IgG and adds biotin tags to its proximal amine groups, enhancing the immunosignal of target proteins. In our experiments, the BioEnhancer system amplified the immunosignal by tenfold compared to the standard western blot. Additionally, our strategy could couple with other signal enhancement methods to further increase the western blot sensitivity. 相似文献
28.
Characterization of multiple fragmentation pathways initiated by collision‐induced dissociation of multifunctional anions formed by deprotonation of 2‐nitrobenzenesulfonylglycine 下载免费PDF全文
Tara E. Tovstiga Elizabeth A. L. Gillis J. Stuart Grossert Robert L. White 《Journal of mass spectrometry : JMS》2014,49(2):168-177
The correlation of anion structure with the fragmentation behavior of deprotonated nitrobenzenesulfonylamino acids was investigated using tandem mass spectrometry, isotopic labeling and computational methods. Four distinct fragmentation pathways resulting from the collision‐induced dissociation (CID) of deprotonated 2‐nitrobenzenesulfonylglycine (NsGly) were characterized. The unusual loss of the aryl nitro substituent as HONO was the lowest energy process. Subsequent successive losses of CO, HCN and SO2 indicated that an ortho cyclization reaction had accompanied loss of HONO. Other pathways involving rearrangement of the ionized sulfonamide group, dual bond cleavage and intramolecular nucleophilic displacement were proposed to account for the formation of phenoxide, arylsulfinate and arylsulfonamide product ions at higher collision energies. The four distinct fragmentation pathways were consistent with precursor–product relationships established by CID experiments, isotopic labeling results and the formation of analogous product ions from 2,4‐dinitrobenzenesulfonylglycine and the Ns derivatives of alanine and 2‐aminoisobutyric acid. The computations confirmed a low barrier for ortho cyclization with loss of HONO and feasible energetics for each reaction step in the four pathways. Computations also indicated that three of the fragmentation pathways started from NsGly ionized at the carboxyl group. Overall, the pathways identified for the fragmentation of the NsGly anion differed from processes reported for anions containing a single functional group, demonstrating the importance of functional group interactions in the fragmentation pathways of multifunctional anions. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
29.
Max Kronenwerth Kenan A. J. Bozhüyük Dr. Astrid S. Kahnt Prof. Dr. Dieter Steinhilber Dr. Sophie Gaudriault Marcel Kaiser Prof. Dr. Helge B. Bode 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(52):17478-17487
Six new lipodepsipeptides and an additional linear derivative named taxlllaids A–G ( 1 – 7 ) have been identified in the entomopathogenic bacterium Xenorhabdus indica. The structures of the main compounds have been solved by detailed NMR spectroscopic analysis and the structures of minor derivatives were elucidated by a combination of labelling experiments and detailed MS experiments. The absolute configuration of the taxlllaids was deduced by using the advanced Marfey method and analysis of the biosynthesis gene cluster showing the presence of epimerisation domains, which was subsequently proved to be correct by solid‐phase peptide synthesis of all taxlllaids. The exchange of a single amino acid in the adenylation domain was shown to be responsible for substrate promiscuity of the third A domain, resulting in the incorporation of leucine, phenylalanine or tyrosine. Bioactivity testing revealed the taxlllaids to be weakly active against Plasmodium falciparum and against a number of eukaryotic cell lines. 相似文献
30.
Zhibo Liu Maral Pourghiasian Mark Alex Radtke Joseph Lau Dr. Jinhe Pan Gemma M. Dias Dr. Donald Yapp Dr. Kuo‐Shyan Lin Prof. Dr. Francois Bénard Prof. Dr. David M. Perrin 《Angewandte Chemie (International ed. in English)》2014,53(44):11876-11880
A new zwitterionic organotrifluoroborate is appended to three radiosynthons that afford undergo facile bioconjugation to several clinically relevant peptides and one enzyme inhibitor. Molecularly complex bioconjugates are 18F‐labeled in a single aqueous step in rapid time (<15 min) without HPLC purification to afford tracers in good yields (>200 mCi, 20–40 %) at high specific activity (≥3 Ci/μmol) and at >98 % purity. PET imaging shows in vivo stability and tumor uptake. 相似文献