全文获取类型
收费全文 | 271篇 |
免费 | 0篇 |
专业分类
化学 | 163篇 |
晶体学 | 1篇 |
力学 | 2篇 |
数学 | 36篇 |
物理学 | 69篇 |
出版年
2022年 | 2篇 |
2020年 | 4篇 |
2018年 | 2篇 |
2016年 | 4篇 |
2014年 | 3篇 |
2013年 | 7篇 |
2012年 | 13篇 |
2011年 | 13篇 |
2010年 | 4篇 |
2009年 | 6篇 |
2008年 | 8篇 |
2007年 | 12篇 |
2006年 | 8篇 |
2005年 | 12篇 |
2004年 | 9篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 13篇 |
2000年 | 9篇 |
1999年 | 4篇 |
1998年 | 5篇 |
1997年 | 2篇 |
1996年 | 6篇 |
1995年 | 5篇 |
1994年 | 6篇 |
1993年 | 5篇 |
1992年 | 3篇 |
1991年 | 8篇 |
1990年 | 4篇 |
1989年 | 4篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 3篇 |
1983年 | 5篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1977年 | 4篇 |
1976年 | 5篇 |
1975年 | 2篇 |
1974年 | 6篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1941年 | 1篇 |
1916年 | 1篇 |
排序方式: 共有271条查询结果,搜索用时 15 毫秒
1.
Dr. Safaa M. Kishk Dr. Kirsty J. McLean Dr. Sakshi Sood Darren Smith Jack W.D. Evans Prof. Mohamed A. Helal Prof. Mohamed S. Gomaa Prof. Ismail Salama Prof. Samia M. Mostafa Dr. Luiz Pedro S. de Carvalho Colin W. Levy Prof. Andrew W. Munro Dr. Claire Simons 《ChemistryOpen》2019,8(7):995-1011
The emergence of untreatable drug-resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (KD). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl ( 10 f ) and tert-butyl ( 10 g ) compounds displaying optimal activity (MIC 1.562 μg/mL, KD 0.22 μM ( 10 f ) and 4.81 μM ( 10 g )). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H-bond acceptors/H-bond donors 4/0, number of rotatable bonds 5–6, molecular volume >340 Å3, topological polar surface area <40 Å2. 相似文献
2.
Dr. Thais F. Abelha Dr. Graeme Morris Dr. Sandro M. Lima Dr. Luis H. C. Andrade Dr. Andrew J. McLean Prof. Cameron Alexander Dr. Jesus Calvo-Castro Dr. Callum J. McHugh 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(14):3173-3180
Development of novel bioimaging materials that exhibit organelle specific accumulation continues to be at the forefront of research interests and efforts. Among the various subcellular organelles, mitochondria, which are found in the cytoplasm of eukaryotic cells, are of particular interest in relation to their vital function. To date, most molecular probes that target mitochondria utilise delocalised lipophilic cations such as triphenylphosphonium and pyridinium. However, the use of such charged motifs is known to be detrimental to the working function of the mitochondrial transmembrane potential and there remains a strong case for development of neutral mitochondrial fluorescent probes. Herein, we demonstrate for the first time the exploitation of diketopyrrolopyrrole-based chemistries for the realisation of a neutral fluorescent probe that exhibits organelle specific accumulation within the mitochondria at the nanomolar level. The synthesised probe, which bears a neutral triphenylphosphine oxide moiety, exhibits a large Stokes shift and high fluorescence quantum yield in water, both highly sought-after properties in the development of bioimaging agents. In vitro studies reveal no interference with cell metabolism when tested for the human MCF7 breast cancer cell and nanomolar subcellular organelle colocalisation with commercially available mitochondrial staining agent Mitotracker Red. In light of its novelty, neutral structure and the preferential accumulation at nanomolar concentrations we anticipate this work to be of significant interest for the increasingly larger community devoted to the realisation of neutral mitochondrial selective systems and more widely to those engaged in the rational development of superior organic architectures in the biological field. 相似文献
3.
4.
We overview our work [7], [8], [9], [10], [11], [6] defining and studying normal crossings varieties and subvarieties in symplectic topology. This work answers a question of Gromov on the feasibility of introducing singular (sub)varieties into symplectic topology in the case of normal crossings singularities. It also provides a necessary and sufficient condition for smoothing normal crossings symplectic varieties. In addition, we explain some connections with other areas of mathematics and discuss a few directions for further research. 相似文献
5.
John A. McLean 《Journal of the American Society for Mass Spectrometry》2009,20(10):1775-1781
Structural separations on the basis of gas-phase ion mobility-mass spectrometry are increasingly used for the analysis of
complex biological samples. As a tool to elucidate biomolecular structure, ion mobility-mass spectrometry methods are unique
in that direct molecular structural information is obtained for all resolved species, largely irrespective of the complexity
of the sample. Computational approaches are used to interpret and discern structural details consistent with the empirical
results. To a first approximation, correlations of mobility with mass allow for qualitative identification of the molecular
class to which a particular species belongs. These correlations allow simultaneous characterization of different classes of
biomolecules, which provides a means for combining omics measurements, such as lipidomics, proteomics, glycomics, and metabolomics,
in the same analysis. Examination of the correlation of fine structure reveals that specific structural motifs, chemical functionality,
chemical connectivity, and composition may also be determined, depending on the specific biomolecular class. Mapping the coarse
and fine structure in ion mobility-mass spectrometry conformation space measurements provides an atlas for interpretation
and discovery in complicated spectra. 相似文献
6.
F. C. McLean und D. D. Van Slyke 《Fresenius' Journal of Analytical Chemistry》1916,55(7):347-348
Ohne Zusammenfassung 相似文献
7.
Saurav S. Sengupta J. Scott Parent J. Keith McLean 《Journal of polymer science. Part A, Polymer chemistry》2005,43(20):4882-4893
Selective graft modifications of polypropylene (PP) are demonstrated in which desirable functionality is introduced without the degradation that accompanies conventional radical‐mediated processes. A range of modification strategies is presented, each exploiting triallyl trimellitate (TATM) or its derivatives to counteract the effects of macroradical fragmentation on the molecular weight. Model compound studies, as well as examinations of atactic PP reaction products, show that allylic ester activation occurs predominately by a radical‐addition/hydrogen‐transfer sequence, with a limited propensity for telomerization. The cografting of TATM and maleic anhydride leads to maleated PP of a high melt viscosity, whereas the apparent incompatibility of TATM with vinyltrimethoxysilane requires the use of TATM‐assisted thiol–ene addition and/or diallyl silane grafting to produce moisture‐curable PP derivatives. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 4882–4893, 2005 相似文献
8.
The merger of transition metal catalysis with visible light photoredox catalysis in a cooperative fashion has recently emerged as a versatile way of developing new synthetic methodologies. This review will focus on the relatively new but fast expanding area of dual copper- and photoredox-catalysis, detailing recent developments in the area. 相似文献
9.
Transgenic plants offer a promising system for large-scale production of therapeutic proteins such as monoclonal antibodies (mAbs). This paper describes a membrane-based process suitable for purification of a humanized mAb expressed in tobacco. Most monoclonal antibody purification schemes rely on the use of Protein A as the affinity ligand for antibody capture. The main objective of our work was to develop non-Protein A-based purification methods to avoid some of the problems and limitations associated with this ligand, e.g. cost, immunotoxicity, and antibody aggregation during elution. Ion exchange membrane chromatography (IEMC) was used for primary capture and preliminary purification of the mAb from tobacco juice. Hydrophobic interaction membrane chromatography (HIMC) was then used for high-resolution purification, followed by ultrafiltration for polishing, desalting and buffer exchange. Using this scheme, both high mAb purity (single peak in size exclusion chromatogram, i.e., ca. 100% purity) and high recovery (77% of mAb spiked into the tobacco extract) were achieved. Membrane chromatography is generally considered unsuitable for resolving bound proteins by gradient elution and is therefore commonly used in the bind and elute mode with a single-step change of mobile phase. We show that the gradient elution process in the HIMC step can be optimized to increase the resolution and thereby obtain product of high purity. 相似文献
10.
Electronically excited iodine atoms, I(52P1/2), have been monitored using time resolved atomic resonance fluorescence. Rate data for quenching by C3H8 and CD4 are presented. 相似文献