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排序方式: 共有336条查询结果,搜索用时 812 毫秒
331.
Yasmin Borutzki Lukas Skos Prof. Christopher Gerner Prof. Samuel M. Meier-Menches 《Chembiochem : a European journal of chemical biology》2023,24(17):e202300178
During recent years, accumulating evidence suggested that metal-based candidate drugs are promising modulators of cytoskeletal and cytoskeleton-associated proteins. This was substantiated by the identification and validation of actin, vimentin and plectin as targets of distinct ruthenium(II)- and platinum(II)-based modulators. Despite this, structural information about molecular interaction is scarcely available. Here, we compile the scattered reports about metal-based candidate molecules that influence the cytoskeleton, its associated proteins and explore their potential to interfere in cancer-related processes, including proliferation, invasion and the epithelial-to-mesenchymal transition. Advances in this field depend crucially on determining binding sites and on gaining comprehensive insight into molecular drug-target interactions. These are key steps towards establishing yet elusive structure-activity relationships. 相似文献
332.
Sabina Deutschmann Lukas Rimle Prof. Dr. Christoph von Ballmoos 《Chembiochem : a European journal of chemical biology》2022,23(2):e202100543
The topological organization of proteins embedded in biological membranes is crucial for the tight interplay between these enzymes and their accessibility to substrates in order to fulfil enzymatic activity. The orientation of a membrane protein reconstituted in artificial membranes depends on many parameters and is hardly predictable. Here, we present a convenient approach to assess this important property independent of the enzymatic activity of the reconstituted protein. Based on cysteine-specific chemical modification of a target membrane protein with a cyanine fluorophore and a corresponding membrane-impermeable fluorescence quencher, the novel strategy allows rapid evaluation of the distribution of the two orientations after reconstitution. The assay has been tested for the respiratory complexes bo3 oxidase and ATP synthase of Escherichia coli and the results agree well with other orientation determination approaches. Given the simple procedure, the proposed method is a powerful tool for optimization of reconstitution conditions or quantitative orientation information prior to functional measurements. 相似文献
333.
Dr. Gareth G. Doherty Geraldine Jia Ming Ler Dr. Norbert Wimmer Prof. Dr. Paul V. Bernhardt Dr. Roger A. Ashmus Prof. David J. Vocadlo Dr. Zachary Armstrong Prof. Gideon J. Davies Dr. Marco Maccarana Prof. Jin-ping Li Yasmin Kayal Prof. Vito Ferro 《Chembiochem : a European journal of chemical biology》2023,24(4):e202200619
1-Azasugar analogues of l -iduronic acid (l -IdoA) and d -glucuronic acid (d -GlcA) and their corresponding enantiomers have been synthesized as potential pharmacological chaperones for mucopolysaccharidosis I (MPS I), a lysosomal storage disease caused by mutations in the gene encoding α-iduronidase (IDUA). The compounds were efficiently synthesized in nine or ten steps from d - or l -arabinose, and the structures were confirmed by X-ray crystallographic analysis of key intermediates. All compounds were inactive against IDUA, although l -IdoA-configured 8 moderately inhibited β-glucuronidase (β-GLU). The d -GlcA-configured 9 was a potent inhibitor of β-GLU and a moderate inhibitor of the endo-β-glucuronidase heparanase. Co-crystallization of 9 with heparanase revealed that the endocyclic nitrogen of 9 forms close interactions with both the catalytic acid and catalytic nucleophile. 相似文献
334.
Angelo G. Giumanini Giancarlo Verardo Sabina Cauci 《Advanced Synthesis \u0026amp; Catalysis》1987,329(3):417-432
Some aliphatic carboxylic anhydrides gave excellent yields of the novel addition products to both aliphatic and aromatic N-methyleneimines, starting from their aliphatic and aromatic trimeric cyclic oligomers. A preliminary positive ion mass spectrometric study is here reported. They hydrolyze surprisingly faster than the corresponding acid amides, making necessary the intervention of a special mechanism. The reduction of the acetylamideester of cyclohexylmethyleneimine ( 3c ) with LiAlH4 was also “abnormal”, as it yielded N-methyl-N-ethylcyclohexylamine in quantitative yield. 相似文献
335.
336.
Danila Boytsov Stefania Brescia Gustavo Chaves Sabina Koefler Christof Hannesschlaeger Christine Siligan Nikolaus Goessweiner-Mohr Boris Musset Peter Pohl 《Small (Weinheim an der Bergstrasse, Germany)》2023,19(16):2205968
The voltage-gated proton channel, HV1, is crucial for innate immune responses. According to alternative hypotheses, protons either hop on top of an uninterrupted water wire or bypass titratable amino acids, interrupting the water wire halfway across the membrane. To distinguish between both hypotheses, the water mobility for the putative case of an uninterrupted wire is estimated. The predicted single-channel water permeability 2.3 × 10−12 cm3 s−1 reflects the permeability-governing number of hydrogen bonds between water molecules in single-file configuration and pore residues. However, the measured unitary water permeability does not confirm the predicted value. Osmotic deflation of reconstituted lipid vesicles reveals negligible water permeability of the HV1 wild-type channel and the D174A mutant open at 0 mV. The conductance of 1400 H+ s−1 per wild-type channel agrees with the calculated diffusion limit for a ≈2 Å capture radius for protons. Removal of a charged amino acid (D174) at the pore mouth decreases H+ conductance by reducing the capture radius. At least one intervening amino acid contributes to H+ conductance while interrupting the water wire across the membrane. 相似文献