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891.
Identification and Optimization of 4‐Anilinoquinolines as Inhibitors of Cyclin G Associated Kinase 下载免费PDF全文
Dr. Christopher R. M. Asquith Prof. Dr. Tuomo Laitinen James M. Bennett Dr. Paulo H. Godoi Dr. Michael P. East Dr. Graham J. Tizzard Prof. Dr. Lee M. Graves Prof. Dr. Gary L. Johnson Ronna E. Dornsife Carrow I. Wells Dr. Jonathan M. Elkins Prof. Dr. Timothy M. Willson Prof. Dr. William J. Zuercher 《ChemMedChem》2018,13(1):48-66
4‐Anilinoquinolines were identified as potent and narrow‐spectrum inhibitors of the cyclin G associated kinase (GAK), an important regulator of viral and bacterial entry into host cells. Optimization of the 4‐anilino group and the 6,7‐quinoline substituents produced GAK inhibitors with nanomolar activity, over 50 000‐fold selectivity relative to other members of the numb‐associated kinase (NAK) subfamily, and a compound (6,7‐dimethoxy‐N‐(3,4,5‐trimethoxyphenyl)quinolin‐4‐amine; 49 ) with a narrow‐spectrum kinome profile. These compounds may be useful tools to explore the therapeutic potential of GAK in prevention of a broad range of infectious and systemic diseases. 相似文献
892.
Cytotoxic Activity and Structure–Activity Relationship of Triazole‐Containing Bis(Aryl Ether) Macrocycles 下载免费PDF全文
Dr. Eduardo Hernández‐Vázquez Dr. Alejandra Chávez‐Riveros Dr. Adriana Romo‐Pérez María Teresa Ramírez‐Apán Dr. Alma D. Chávez‐Blanco Dr. Rocío Morales‐Bárcenas Dr. Alfonso Dueñas‐González Dr. Luis D. Miranda 《ChemMedChem》2018,13(12):1193-1209
Cancer continues to be a worldwide health problem. Certain macrocyclic molecules have become attractive therapeutic alternatives for this disease because of their efficacy and, frequently, their novel mechanisms of action. Herein, we report the synthesis of a series of 20‐, 21‐, and 22‐membered macrocycles containing triazole and bis(aryl ether) moieties. The compounds were prepared by a multicomponent approach from readily available commercial substrates. Notably, some of the compounds displayed interesting cytotoxicity against cancer (PC‐3) and breast (MCF‐7) cell lines, especially those bearing an aliphatic or a trifluoromethyl substituent on the N‐phenyl moiety (IC50<13 μm ). Additionally, some of the compounds were able to induce apoptosis relative to the solvent control; in particular, (Z)‐N‐cyclohexyl‐7‐oxo‐6‐[4‐(trifluoromethyl)phenyl]‐11H‐3,10‐dioxa‐6‐aza‐1(4,1)‐triazola‐4(1,3),9(1,4)‐dibenzenacyclotridecaphane‐5‐carboxamide ( 12 f ) was the most potent in this regard (22.7 % of apoptosis). 相似文献
893.
Synthesis and Evaluation of the Anticancer and Trypanocidal Activities of Boronic Tyrphostins 下载免费PDF全文
Noemi de J. Hiller Nayane A. A. e Silva Dr. Robson X. Faria Dr. André Luís A. Souza Dr. Jackson A. L. C. Resende André Borges Farias Dr. Nelilma Correia Romeiro Dr. Daniela de Luna Martins 《ChemMedChem》2018,13(14):1395-1404
Molecules containing an (cyanovinyl)arene moiety are known as tyrphostins because of their ability to inhibit proteins from the tyrosine kinase family, an interesting target for the development of anticancer and trypanocidal drugs. In the present work, (E)‐(cyanovinyl)benzeneboronic acids were synthesized by Knoevenagel condensations without the use of any catalysts in water through a simple protocol that completely avoided the use of organic solvents in the synthesis and workup process. The in vitro anticancer and trypanocidal activities of the synthesized boronic acids were also evaluated, and it was discovered that the introduction of the boronic acid functionality improved the activity of the boronic tyrphostins. In silico target fishing with the use of a chemogenomic approach suggested that tyrosine‐phosphorylation‐regulated kinase 1a (DYRK1A) was a potential target for some of the designed compounds. 相似文献
894.
895.
Cover Feature: Discovery of Benzimidazole–Quinolone Hybrids as New Cleaving Agents toward Drug‐Resistant Pseudomonas aeruginosa DNA (ChemMedChem 10/2018) 下载免费PDF全文
896.
Synthesis and Evaluation of a Series of Bis(pentylpyridinium) Compounds as Antifungal Agents 下载免费PDF全文
Dr. Daniel Obando Dr. Yasuko Koda Namfon Pantarat Dr. Sophie Lev Dr. Xiaoming Zuo Johanes Bijosono Oei Dr. Fred Widmer Prof. Julianne T. Djordjevic Prof. Tania C. Sorrell Prof. Katrina A. Jolliffe 《ChemMedChem》2018,13(14):1421-1436
A series of bis(4‐pentylpyridinium) compounds with a variety of spacers between the pyridinium headgroups was synthesised, and the antifungal activity of these compounds was investigated. Lengthening the alkyl spacer between the pentylpyridinium headgroups from 12 to 16 methylene units resulted in increased antifungal activity against C. neoformans and C. albicans, but also resulted in increased hemolytic activity and cytotoxicity against mammalian cells. However, inclusion of an ortho‐substituted benzene ring in the centre of the alkyl spacer resulted in decreased cytotoxicity and hemolytic activity, while maintaining antifungal potency. Replacement of the alkyl and aromatic‐containing spacers by more hydrophilic ethylene glycol groups resulted in a loss of antifungal activity. Some of the compounds inhibited fungal PLB1 activity, but the low correlation of this inhibition with antifungal potency indicates PLB1 inhibition is unlikely to be the predominant mode of antifungal action of this class of compounds, with preliminary studies suggesting they may act via disruption of fungal mitochondrial function. 相似文献
897.
Brain‐Penetrant Triazolopyrimidine and Phenylpyrimidine Microtubule Stabilizers as Potential Leads to Treat Human African Trypanosomiasis 下载免费PDF全文
Dr. Ludovica Monti Steven C Wang Dr. Killian Oukoloff Dr. Amos B. Smith III Dr. Kurt R. Brunden Dr. Conor R. Caffrey Dr. Carlo Ballatore 《ChemMedChem》2018,13(17):1751-1754
In vitro whole‐organism screens of Trypanosoma brucei with representative examples of brain‐penetrant microtubule (MT)‐stabilizing agents identified lethal triazolopyrimidines and phenylpyrimidines with sub‐micromolar potency. In mammalian cells, these antiproliferative compounds disrupt MT integrity and decrease total tubulin levels. Their parasiticidal potency, combined with their generally favorable pharmacokinetic properties, which include oral bioavailability and brain penetration, suggest that these compounds are potential leads against human African trypanosomiasis. 相似文献
898.
This review provides a brief summary of the recent research developments in the fabrication and application of conducting polymer nanostructures and their derivatives as electrodes for flexible supercapacitors (SCs). By controlling the nucleation and growth process of polymerization, conducting polymers (CPs) with different nanostructures can be prepared by employing chemical polymerization, electrochemical polymerization and photo-induced polymerization. These CPs (such as polyaniline and polypyrrole) with special nanostructures possess high capacitance, superior rate capability ascribed to large electrochemical surface, and optimal ion diffusion path in the ordered nanostructures. The composites of nano-structured conducting polymer and some conductive flexible substrates (such as carbon nanotube film and graphene film) are proved to be ideal electrode materials for high performance flexible SCs. Furthermore, high N-containing CPs are very prospective for preparing N-doped carbon materials used as flexible electrodes for flexible SCs. With respect to the extra pseudo-capacitance induced by N atoms and superior stability derived from the conjugated graphitic structure of carbon materials, the obtained flexible SCs based on N-doped carbon materials could achieve high capacitance, high rate performance, and superior cycling stability. 相似文献
899.
Mokhtar Guissous Yveline Le Dréau Hasna Boulkhroune Toufik Madani Jacques Artaud 《Journal of the American Oil Chemists' Society》2018,95(3):267-281
Differences in triacylglycerol, fatty acid, squalene, and tocopherol compositions were demonstrated between 8 varieties of virgin olive oils (Aberkane, Aguenaou, Aharoun, Aimel, Bouchouk Guergour, Bouichret, Chemlal, and Sigoise) from Petite Kabylie area, north eastern Algeria. Fatty acid and triacylglycerol morphotypes characterized each variety. A principal component analysis, based on triacylglycerol, fatty acid, and squalene compositions, differentiates between varieties. Minor fatty acids and squalene, usually not taken into account individually in authentication studies, are strongly involved in this differentiation, whereas the discriminant power of tocopherols is weak. Soft Independent Modeling of Class Analogy classification using chemical compositions as variables showed a high potential to authenticate the varietal origin of Algerian virgin olive oils. 相似文献
900.
During thermochemical conversion of biological material in a fluidized bed reactor the nutrients are remaining as dust in the product gas. Hot gas filtration represents a possibility to recover these minerals. The characteristics of this gas add up new technical tasks. The following article gives an account of long lasting experience of operation and optimization in a pilot plant. 相似文献