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301.
Anna Di Fiore Simona Maria Monti Alessio Innocenti Jean-Yves Winum Giuseppina De Simone Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2010,20(12):3601-3605
We investigated the inhibition of carbonic anhydrase (CA, EC 4.2.1.1) isoforms I–XV with 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfamide and other simple or sugar sulfamides, a class of less investigated CA inhibitors (CAIs). The crystal structure of the adduct of hCA II with the boron-substituted sulfamide shows the organic scaffold of this compound bound in the hydrophilic half of the active site where it makes a large number of van der Waals contacts with Ile91, Gln92, Val121, Phe131, Leu198, and Thr200. The data here reported provide further insights into sulfamide binding mechanism confirming that this zinc-binding group could be usefully exploited for obtaining new potent and selective CAIs. 相似文献
302.
Francesca Viparelli Simona Maria Monti Giuseppina De Simone Alessio Innocenti Andrea Scozzafava Yan Xu François M.M. Morel Claudiu T. Supuran 《Bioorganic & medicinal chemistry letters》2010,20(16):4745-4748
We investigated the catalytic activity and inhibition of both the zinc and cadmium-containing R1 fragment of the ζ-class carbonic anhydrase (CA, EC 4.2.1.1) from the marine diatom Thalassiosira weissflogii. Our data prove that these enzymes are not only very efficient catalysts for the physiological reaction, but also sensitive to sulfonamide and anion inhibitors, with inhibition constants from the nanomolar to millimolar range. Acetazolamide inhibited the two enzymes with KIs in the range of 58–92 nM. The best anion inhibitors of Cd-R1 were thiocyanate, sulfamate and sulfamide, with KIs of 10–89 μM, whereas the best Zn-R1 anion inhibitors were sulfamate and sulfamide with KIs of 60–72 μM. These enzymes were only weakly inhibited by chloride, bromide or sulfate, main anion components of sea water, with inhibition constants in the range of 0.24–0.85 mM. Thus, similarly to CAs belonging to other classes, the ζ-class CA (with either cadmium or zinc ions at the active site) was inhibited by both anions and sulfonamides. 相似文献
303.
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305.
Maud Hertzog Francesca Milanesi Larnele Hazelwood Andrea Disanza HongJun Liu Emilie Perlade Maria Grazia Malabarba Sebastiano Pasqualato Alessio Maiolica Stefano Confalonieri Christophe Le Clainche Nina Offenhauser Jennifer Block Klemens Rottner Pier Paolo Di Fiore Marie-France Carlier Niels Volkmann Dorit Hanein Giorgio Scita 《PLoS biology》2010,8(6)
Actin capping and cross-linking proteins regulate the dynamics and architectures
of different cellular protrusions. Eps8 is the founding member of a unique
family of capping proteins capable of side-binding and bundling actin filaments.
However, the structural basis through which Eps8 exerts these functions remains
elusive. Here, we combined biochemical, molecular, and genetic approaches with
electron microscopy and image analysis to dissect the molecular mechanism
responsible for the distinct activities of Eps8. We propose that bundling
activity of Eps8 is mainly mediated by a compact four helix bundle, which is
contacting three actin subunits along the filament. The capping activity is
mainly mediated by a amphipathic helix that binds within the hydrophobic pocket
at the barbed ends of actin blocking further addition of actin monomers.
Single-point mutagenesis validated these modes of binding, permitting us to
dissect Eps8 capping from bundling activity in vitro. We further showed that the
capping and bundling activities of Eps8 can be fully dissected in vivo,
demonstrating the physiological relevance of the identified Eps8
structural/functional modules. Eps8 controls actin-based motility through its
capping activity, while, as a bundler, is essential for proper intestinal
morphogenesis of developing Caenorhabditis elegans. 相似文献
306.
Trabelsi D Pini F Bazzicalupo M Biondi EG Aouani ME Mengoni A 《Molecular ecology resources》2010,10(1):170-172
The development of a species-specific marker for the analysis of the genetic polymorphism of the nitrogen-fixing symbiotic bacterium Sinorhizobium meliloti directly from environmental DNA is reported. The marker is based on terminal-restriction fragment length polymorphism (T-RFLP) methodology targeting specifically the 16S-23S Ribosomal Intergenic Spacer of S. meliloti. Species-specificity and polymorphism of the marker were tested on DNA extracted from soil samples and from a collection of 130 S. meliloti bacterial isolates. These primers and the T-RFLP approach proved useful for the detection and analysis of polymorphism of S. meliloti populations. 相似文献
307.
Elisa?Giuntini Marco?Bazzicalupo Maurizio?Castaldini Arturo?Fabiani Nerino?Miclaus Raimondo?Piccolo Giancarlo?Ranalli Francesca?Santomassimo Stefano?Zanobini Alessio?MengoniEmail author 《Annals of microbiology》2006,56(2):83
The industrial production of olive oil is accompanied by the accumulation of large quantities of by-products from the olive milling industry that are commonly dispersed as fertilisers, which are nowadays suspected to have potential toxic effects on is omicroflora. The aim of this work has been the investigation of the genetic diversity of bacterial communities present in soil treated with olive husks focusing on the dinitrogen-fixing bacteria.nifH genes were amplified from total soil DNA using universal primers, cloned and typed by restriction analysis and sequencing of representative haplotypes. On the same samples, DGGE analysis on amplified 16S rDNA was performed aiming at monitoring modifications in the total community pattern. Results showed a high genetic diversity ofnifH genes within the community, which was well in agreement with the total community profiles obtained by DGGE on 16SrDNA. Most of thenifH gene fragments (19 out of 32) were found to be similar to sequences related with clostridia. 相似文献
308.
Ultrastructure of long-range transport carriers moving from the trans Golgi network to peripheral endosomes 总被引:2,自引:0,他引:2
Polishchuk RS San Pietro E Di Pentima A Teté S Bonifacino JS 《Traffic (Copenhagen, Denmark)》2006,7(8):1092-1103
The delivery of mannose 6-phosphate receptors carrying lysosomal hydrolases from the trans-Golgi network (TGN) to the endosomal system is mediated by selective incorporation of the receptor-hydrolase complexes into vesicular transport carriers (TCs) that are coated with clathrin and the adaptor proteins, GGA and AP-1. Previous electron microscopy (EM) and biochemical studies have shown that these TCs consist of spherical coated vesicles with a diameter of 60-100 nm. The use of fluorescent live cell imaging, however, has revealed that at least some of this transport relies on a subset of apparently larger and highly pleiomorphic carriers that detach from the TGN and translocate toward the peripheral cytoplasm until they meet with distally located endosomes. The ultrastructure of such long-range TCs has remained obscure because of the inability to examine by conventional EM the morphological details of rapidly moving organelles. The recent development of correlative light-EM has now allowed us to obtain ultrastructural 'snapshots' of these TCs immediately after their formation from the TGN in live cells. This approach has revealed that such carriers range from typical 60- to 100-nm clathrin-coated vesicles to larger, convoluted tubular-vesicular structures displaying several coated buds. We propose that this subset of TCs serve as vehicles for long-range distribution of biosynthetic or recycling cargo from the TGN to the peripheral endosomes. 相似文献
309.
310.
NO-donors block Plasmodium, Trypanosoma, and Leishmania life cycle by inactivating parasite enzymes, e.g., cysteine proteinases. In this study, the inactivation of falcipain, cruzipain, and Leishmania infantum cysteine proteinase by the NO-donor 4-(phenylsulfonyl)-3-((2-(dimethylamino)ethyl)thio)-furoxan oxalate (SNO-102) is reported. SNO-102 inactivates dose- and time-dependently parasite cysteine proteinases; one equivalent of NO, released from SNO-102, inactivates one equivalent of L. infantum cysteine proteinase. With SNO-102 in excess over the parasite cysteine proteinase, the time course of enzyme inhibition corresponds to a pseudo-first-order reaction for more than 90% of its course. The concentration dependence of the pseudo-first-order rate constant is second-order at low SNO-102 concentration but tends to first-order at high NO-donor concentration. This behavior may be explained by a relatively fast pre-equilibrium followed by a limiting pseudo-first order process. Kinetic parameters of L. infantum cysteine proteinase inactivation by SNO-102 are affected by the acidic pK shift of one apparent ionizing group (from pK(unl)=5.8 to pK(lig)=4.7) upon enzyme inhibition. Falcipain, cruzipain and L. infantum cysteine proteinase inactivation is prevented and reversed by dithiothreitol and L-ascorbic acid. Furthermore, the fluorogenic substrate N-alpha-benzyloxycarbonyl-Phe-Arg-(7-amino-4-methylcoumarin) protects parasite cysteine proteinases from inactivation by SNO-102. The absorption spectrum of the inactive S-nitrosylated SNO-102-treated L. infantum cysteine proteinase displays a maximum at about 340 nm. These results indicate that the parasite cysteine proteinase inactivation by SNO-102 occurs via the NO-mediated S-nitrosylation of the Cys25 catalytic residue. 相似文献