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21.
Isaac O. Donkor Rajesh Devraj Sherry F. Queener Louis R. Barrows Aleem Gangjee 《Journal of heterocyclic chemistry》1996,33(6):1653-1661
A series of diaminobenzo[f]- and diaminobenzo[h]pyrimido[4,5-b]quinolines 1–11 were designed as 5-deaza tetracyclic nonclassical, lipophilic antifolates. The compounds were designed as conformationally semi-rigid and rigid analogs of 2,4-diamino-6-phenyl- 12 and 2,4-diamino-7-phenylpyrido[2,3-d]pyrimidines 13 and 14 . The target compounds were synthesized by cyclocondensation of chlorovinyl aldehydes obtained from appropriately substituted 1- or 2-tetralone, with 2,4,6-friaminopyrimidine. Compounds 1–11 were evaluated as inhibitors of P. carinii and T. gondii dihydrofolate reductases. These pathogens cause fatal opportunistic infections in AIDS patients. In addition, the selectivity of these agents was evaluated using rat liver dihydrofolate reductase as the mammalian source. In general the benzo[f]pyrimido[4,5-b]quinolines 1–5 were more potent than the corresponding benzo[h]pyrimido[4,5-b]quinoline analogues 6–11 against P. carinii and rat liver dihydrofolate reductase and were equipotent against T. gondii dihydrofolate reductase. Compounds 6–11 were moderately selective towards T. gondii dihydrofolate reductase with IC50S in the 10−7 M range. In contrast analogues 1–5 lacked selectivity against P. carinii or T. gondii dihydrofolate reductase and were, in general, potent inhibitors of rat liver dihydrofolate reductase with IC50S in the 10−8 M range. Analogues 1 and 4 were evaluated against a series of tumor cell lines in vitro and were found to have moderate antitumor activity (IC50 10−6 M). The structure activity/selectivity relationships suggest that benzo[f]pyrimido analogues 1–5 with the phenyl ring substitution in the “upper” portion of the tetracyclic ring are better accommodated within the rat liver (mammalian) dihydrofolate reductase and P. carinii dihydrofolate reductase active sites compared to the benzo[h]pyrimido analogues 6–11 which have the phenyl ring substitution in the “lower” portion of the tetracyclic ring. In contrast T. gondii dihydrofolate reductase does not discriminate between the isomers and binds to both series of compounds with similar affinities. 相似文献
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DOTA-tetraamide ligands having extended phenol or pyridine substituents have been synthesized. The (5)D(0) --> (7)F(J) deltaJ = 1 and 2 emission bands in the corresponding europium(III) complexes differ in their sensitivity to solution pH. This offers the potential for developing pH responsive probes for in vivo imaging that are independent of probe concentration. 相似文献
24.
Chemler SR Trauner D Danishefsky SJ 《Angewandte Chemie (International ed. in English)》2001,40(24):4544-4568
The development of new reactions that facilitate the creative and efficient synthesis of molecular structures with desirable properties continues to fascinate chemists. The test of a significant contribution is its acceptance over time by the scientific community. The B-alkyl Suzuki-Miyaura cross-coupling reaction appears to be one such reaction. Since its disclosure by Suzuki and Miyaura in 1986, this reaction has been an attractive solution to challenging synthetic problems. 相似文献
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Moreno KX Harrison C Sherry AD Malloy CR Merritt ME 《Journal of magnetic resonance (San Diego, Calif. : 1997)》2011,213(1):187-191
Nuclei with long T1s are optimal targets for dynamic nuclear polarization (DNP). Therefore, most of the agents used in metabolic imaging and spectroscopy studies are based on carboxylic acid moieties that lack protons, a strong source of dipolar relaxation. Metabolic flux information encoded into spectra of small molecule metabolites in the form of the 13C isotopomer data cannot be accessed using standard 13C hyperpolarization methods because protonated carbons relax too quickly through T1 dipolar relaxation. It is shown here that the longitudinal mixing sequence FLOPSY-8 can be used to transfer polarization from a long T1 storage nucleus to adjacent protonated carbons so that they may be detected with high sensitivity. We demonstrate that FLOPSY-8 allows a direct readout of isotopomer populations in butyrate and glutamate in vitro. 相似文献
27.
The test cell constitutes the core functionality of a permeation testing system. Accuracy of an experimental methodology depends on the ability of the test cell to efficiently deliver the challenge agents to the test material, collect all the transported permeate compounds from the test material and transfer those analytes to the online detector. Common test cell designs used in the US and internationally form the basis of their respective testing procedures. However, widespread usage does not necessarily equate to defensible assurance of analytical reliability. Consequently, chemical protective materials characterized with these cells may provide inadequate protection to users whose health and safety depend on barrier garments such as gloves and suits. Permeation test data, including those acquired in our laboratory, have emphasized the significance of test cell design on the accuracy of permeation measurements. This paper describes the key considerations necessary to ensure analytical reliability for a test cell, illustrates quantitative improvements demonstrated by existing prototypes and, finally, proposes a design which further advances the technology of permeation testing. 相似文献
28.
EVIDENCE FOR AN ULTRAVIOLET SUNSCREEN ROLE OF THE EXTRACELLULAR PIGMENT SCYTONEMIN IN THE TERRESTRIAL CYANOBACTERIUM Chiorogloeopsis sp. 总被引:2,自引:0,他引:2
Ferran Garcia-Pichel Nelson D. Sherry Richard W. Castenholz 《Photochemistry and photobiology》1992,56(1):17-23
The proposed photoprotective role of the UV-A absorbing, extracellular pigment scytonemin was studied in the terrestrial cyanobacterium Chlorogloeopsis sp. strain O-89-Cgs(1). UV-A (315-400 nm) caused growth delay, cell growth restarting only when scytonemin had accumulated in the extracellular envelopes. Cultures with scytonemin were more resistant to photoinhibition of photosynthesis than cultures without scytonemin, the differential resistance being much greater to UV-A-caused photoinhibition than to photoinhibition caused by visible light. The presence of scytonemin in the extracellular envelopes was correlated with the inability of UV-A radiation to induce strong photopigment fluorescence (685 nm emission), regardless of the specific content os photosynthetic pigments. The physical removal of the scytonemin containing extracellular envelopes brought about the loss of UV-A resistance as measured by photobleaching rates of chlorophyll a under conditions of physiological inactivity (desiccation). These observations provide strong evidence for the proposed protective role of scytonemin, as a passive UV-A sunscreen, in cyanobacteria. 相似文献
29.
G. C. Sherry 《Foundations of Physics》1989,19(6):733-741
Several versions exist of pseudo-classical models of the electron using Grassmann variables. Most of these require additional constraints on the variables, and it is these which, when quantized, lead to Dirac's equation. In addition, the Grassmann variables do not have physical interpretations. In this article a model is constructed which does not require constraints and in which the Grassmann variables can be interpreted as observables. Dirac's equation is obtained directly from quantization. 相似文献
30.