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951.
Aurachins, a family of isoprenoid quinoline alkaloids isolated from the myxobacterium Stigmatella aurantiaca, possess multiple interesting bioactivities and were subject of intensive studies of biosynthesis. In this Letter, we describe the efficient few step total synthesis of the parent compound aurachin D and two isoprenoid analogues via Conrad–Limpach cyclization. The main antimicrobial and cytotoxic profiles of these derivatives were explored. 相似文献
952.
Lisa Moni Alberto Marra Jerauld S. Skotnicki Frank E. Koehn Magid Abou-Gharbia Alessandro Dondoni 《Tetrahedron letters》2013
The conversion of the C40 secondary hydroxyl group of rapamycin into the azido group was followed by copper catalyzed cycloaddition of the resulting azido-rapamcin with various unprotected propargyl O- and S-glycosides and a C-ethynyl derivative. This approach furnished a collection of triazole-bridged rapamycin glycoconjugates (14 examples) in 44–83% isolated yield. 相似文献
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954.
Binbin Tu Lisa Diestel Zhao‐Lin Shi W. R. L. Nisansala Bandara Yi Chen Weimin Lin Yue‐Biao Zhang Shane G. Telfer Qiaowei Li 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2019,131(16):5402-5407
Positioning a diverse set of building blocks in a well‐defined array enables cooperativity amongst them and the systematic programming of functional properties. The extension of this concept to porous metal–organic frameworks (MOFs) is challenging since the installation of multiple components in a well‐ordered framework requires careful design of the lattice topology, judicious selection of building blocks, and precise control of the crystallization parameters. Herein, we report how we met these challenges to prepare the first quinary MOF structure, FDM‐8, by bottom‐up self‐assembly from two metals, ZnII and CuI, and three distinct carboxylate‐ and pyrazolate‐based linkers. With a surface area of 3643 m2 g?1, FDM‐8 contains hierarchical pores and shows outstanding methane‐storage capacity at high pressure. Furthermore, functional groups introduced on the linkers became compartmentalized in predetermined arrays in the pores of the FDM‐8 framework. 相似文献
955.
We consider nonuniformly elliptic variational problems and give optimal conditions guaranteeing the local Lipschitz regularity of solutions in terms of the regularity of the given data. The analysis catches the main model cases in the literature. Integrals with fast, exponential-type growth conditions as well as integrals with unbalanced polynomial growth conditions are covered. Our criteria involve natural limiting function spaces and reproduce, in this very general context, the classical and optimal ones known in the linear case for the Poisson equation. Moreover, we provide new and natural growth a priori estimates whose validity was an open problem. Finally, we find new results also in the classical uniformly elliptic case. Beyond the specific results, the paper proposes a new approach to nonuniform ellipticity that, in a sense, allows us to reduce nonuniform elliptic problems to uniformly elliptic ones via potential theoretic arguments that are for the first time applied in this setting. © 2019 the Authors. Communications on Pure and Applied Mathematics is published by the Courant Institute of Mathematical Sciences and Wiley Periodicals, Inc. 相似文献
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957.
Andreas Faust Nicole Bumer Alina Schlütermann Manuel Becht Lilo Greune Christiane Geyer Christian Rüter Renato Margeta Lisa Wittmann Petra Dersch Georg Lenz Wolfgang E. Berdel Sebastian Bumer 《Angewandte Chemie (International ed. in English)》2022,61(1):e202109769
Ibrutinib is an inhibitor of Bruton's tyrosine kinase that has been approved for the treatment of patients with chronic lymphocytic leukemia, mantle cell lymphoma and Waldenstrom's macroglobulinemia and is connected with toxicities. To minimize its toxicities, we linked ibrutinib to a cell-targeted, internalizing antibody. To this end, we synthesized a poly-anionic derivate, ibrutinib-Cy3.5, that retains full functionality. This anionic inhibitor is complexed by our anti-CD20-protamine targeting conjugate and free protamine, and thereby spontaneously assembles into an electrostatically stabilized vesicular nanocarrier. The complexation led to an accumulation of the drug driven by the CD20 antigen internalization to the intended cells and an amplification of its pharmacological effectivity. In vivo, we observed a significant enrichment of the drug in xenograft lymphoma tumors in immune-compromised mice and a significantly better response to lower doses compared to the original drug. 相似文献
958.
Determination of GDC‐0980 (apitolisib), a small molecule dual phosphatidylinositide 3‐kinase/mammalian target of rapamycin inhibitor in dog plasma by LC‐MS/MS to support a GLP toxicology study
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Xiao Ding Laurent Salphati Amy Kim Eric Morinello Lisa Wong Jodie Pang Shaundel Percey Min Meng Scott Reuschel Brian Dean 《Biomedical chromatography : BMC》2015,29(8):1274-1279
An LC‐MS/MS method for the determination of GDC‐0980 (apitolisib) concentrations in dog plasma has been developed and validated for the first time to support pre‐clinical drug development. Following protein precipitation with acetonitrile, the resulting samples were analyzed using reverse‐phase chromatography on a Metasil AQ column. The mass analysis was performed on a triple quadruple mass spectrometer coupled with an electrospray interface in positive ionization mode. The selected reaction monitoring transitions monitored were m/z 499.3 → 341.1 for GDC‐0980 and m/z 507.3 → 341.1 for IS. The method was validated over the calibration curve range 0.250–250 ng/mL with linear regression and 1/x2 weighting. Relative standard deviation (RSD) ranged from 0.0 to 10.9% and accuracy ranged from 93.4 to 113.6% of nominal. Stable‐labeled internal standard GDC‐0980‐d8 was used to minimize matrix effects. This assay was used for the measurement of GDC‐0980 dog plasma concentrations to determine toxicokinetic parameters after oral administration of GDC‐0980 (0.03, 0.1 and 0.3 mg/kg) to beagle dogs in a GLP toxicology study. Peak concentration ranged from 3.23 to 84.9 ng/mL. GDC‐0980 was rapidly absorbed with a mean time to peak concentration ranging from 1.3 to 2.4 h. Mean area under the concentration–time curve from 0 to 24 hours ranged from 54.4 to 542 ng h/mL. Copyright © 2015 John Wiley & Sons, Ltd. 相似文献
959.
Muresan Emil Ioan Lutic Doina Lisa Gabriela Pui Aurel 《Journal of Sol-Gel Science and Technology》2017,81(3):934-944
Journal of Sol-Gel Science and Technology - Porous aluminosilicate macrospheres were prepared by spray gelling technique using chitosan, chitosan and yeast cells and respectively chitosan, yeast... 相似文献
960.