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1.
Virginia Veronica Visconti Ida Cariati Simona Fittipaldi Riccardo Iundusi Elena Gasbarra Umberto Tarantino Annalisa Botta 《International journal of molecular sciences》2021,22(8)
DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions. 相似文献
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María García-álvaro Annalisa Addante Cesáreo Roncero Margarita Fernández Isabel Fabregat Aránzazu Sánchez Blanca Herrera 《International journal of molecular sciences》2015,16(9):20431-20448
The study of bone morphogenetic proteins (BMPs) role in tumorigenic processes, and specifically in the liver, has gathered importance in the last few years. Previous studies have shown that BMP9 is overexpressed in about 40% of hepatocellular carcinoma (HCC) patients. In vitro data have also shown evidence that BMP9 has a pro-tumorigenic action, not only by inducing epithelial to mesenchymal transition (EMT) and migration, but also by promoting proliferation and survival in liver cancer cells. However, the precise mechanisms driving these effects have not yet been established. In the present work, we deepened our studies into the intracellular mechanisms implicated in the BMP9 proliferative and pro-survival effect on liver tumor cells. In HepG2 cells, BMP9 induces both Smad and non-Smad signaling cascades, specifically PI3K/AKT and p38MAPK. However, only the p38MAPK pathway contributes to the BMP9 growth-promoting effect on these cells. Using genetic and pharmacological approaches, we demonstrate that p38MAPK activation, although dispensable for the BMP9 proliferative activity, is required for the BMP9 protective effect on serum withdrawal-induced apoptosis. These findings contribute to a better understanding of the signaling pathways involved in the BMP9 pro-tumorigenic role in liver tumor cells. 相似文献
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The Fight against the Influenza A Virus H1N1: Synthesis,Molecular Modeling,and Biological Evaluation of Benzofurazan Derivatives as Viral RNA Polymerase Inhibitors 下载免费PDF全文
Dr. Mafalda Pagano Dr. Daniele Castagnolo Dr. Martina Bernardini Anna Lucia Fallacara Ilaria Laurenzana Davide Deodato Dr. Ulrich Kessler Dr. Beatrice Pilger Dr. Lilli Stergiou Dr. Stephan Strunze Dr. Cristina Tintori Prof. Maurizio Botta 《ChemMedChem》2014,9(1):129-150
The influenza RNA polymerase complex, which consists of the three subunits PA, PB1, and PB2, is a promising target for the development of new antiviral drugs. A large library of benzofurazan compounds was synthesized and assayed against influenza virus A/WSN/33 (H1N1). Most of the new derivatives were found to act by inhibiting the viral RNA polymerase complex through disruption of the complex formed between subunits PA and PB1. Docking studies were also performed to elucidate the binding mode of benzofurazans within the PB1 binding site in PA and to identify amino acids involved in their mechanism of action. The predicted binding pose is fully consistent with the biological data and lays the foundation for the rational development of more effective PA–PB1 inhibitors. 相似文献
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Immacolata Ruggiero Monica Terracciano Nicola M Martucci Luca De Stefano Nunzia Migliaccio Rosarita Tatè Ivo Rendina Paolo Arcari Annalisa Lamberti Ilaria Rea 《Nanoscale research letters》2014,9(1):329
Diatomite is a natural fossil material of sedimentary origin, constituted by fragments of diatom siliceous skeletons. In this preliminary work, the properties of diatomite nanoparticles as potential system for the delivery of drugs in cancer cells were exploited. A purification procedure, based on thermal treatments in strong acid solutions, was used to remove inorganic and organic impurities from diatomite and to make them a safe material for medical applications. The micrometric diatomite powder was reduced in nanoparticles by mechanical crushing, sonication, and filtering. Morphological analysis performed by dynamic light scattering and transmission electron microscopy reveals a particles size included between 100 and 300 nm. Diatomite nanoparticles were functionalized by 3-aminopropyltriethoxysilane and labeled by tetramethylrhodamine isothiocyanate. Different concentrations of chemically modified nanoparticles were incubated with cancer cells and confocal microscopy was performed. Imaging analysis showed an efficient cellular uptake and homogeneous distribution of nanoparticles in cytoplasm and nucleus, thus suggesting their potentiality as nanocarriers for drug delivery.
PACS
87.85.J81.05.Rm; 61.46. + w 相似文献8.
Kuwanon‐L as a New Allosteric HIV‐1 Integrase Inhibitor: Molecular Modeling and Biological Evaluation 下载免费PDF全文
Dr. Francesca Esposito Dr. Cristina Tintori Dr. Riccardo Martini Dr. Frauke Christ Prof. Zeger Debyser Roberto Ferrarese Dr. Gianluigi Cabiddu Dr. Angela Corona Dr. Elisa Rita Ceresola Dr. Andrea Calcaterra Dr. Valentina Iovine Prof. Bruno Botta Dr. Massimo Clementi Dr. Filippo Canducci Prof. Maurizio Botta Prof. Enzo Tramontano 《Chembiochem : a European journal of chemical biology》2015,16(17):2507-2512
HIV‐1 integrase (IN) active site inhibitors are the latest class of drugs approved for HIV treatment. The selection of IN strand‐transfer drug‐resistant HIV strains in patients supports the development of new agents that are active as allosteric IN inhibitors. Here, a docking‐based virtual screening has been applied to a small library of natural ligands to identify new allosteric IN inhibitors that target the sucrose binding pocket. From theoretical studies, kuwanon‐L emerged as the most promising binder and was thus selected for biological studies. Biochemical studies showed that kuwanon‐L is able to inhibit the HIV‐1 IN catalytic activity in the absence and in the presence of LEDGF/p75 protein, the IN dimerization, and the IN/LEDGF binding. Kuwanon‐L also inhibited HIV‐1 replication in cell cultures. Overall, docking and biochemical results suggest that kuwanon‐L binds to an allosteric binding pocket and can be considered an attractive lead for the development of new allosteric IN antiviral agents. 相似文献
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Identification of Aminoimidazole and Aminothiazole Derivatives as Src Family Kinase Inhibitors 下载免费PDF全文
Dr. Cinzia Maria Francini Dr. Anna Lucia Fallacara Dr. Roberto Artusi Dr. Laura Mennuni Dr. Alessia Calgani Dr. Adriano Angelucci Prof. Silvia Schenone Prof. Maurizio Botta 《ChemMedChem》2015,10(12):2027-2041
Src family kinases (SFKs) are a family of non‐receptor tyrosine kinases (TKs) implicated in the regulation of many cellular processes. The aberrant activity of these TKs has been associated with the growth and progression of cancer. In particular, c‐Src is overexpressed or hyperactivated in a variety of solid tumors and is most likely a strong promoting factor for the development of metastasis. Herein, the synthesis of new 4‐aminoimidazole and 2‐aminothiazole derivatives and their in vitro biological evaluation are described for their potential use as SFK inhibitors. Initially, 2‐aminothiazole analogues of dasatinib and 4‐aminoimidazole derivatives were synthesized and tested against the SFKs Src, Fyn, Lyn, and Yes. Five hits were identified as the most promising compounds, with Ki values in the range of 90–480 nm . A combination of molecular docking, homology modeling, and molecular dynamics were then used to investigate the possible binding mode of such compounds within the ATP binding site of the SFKs. Finally, the antiproliferative activities of the best candidates were evaluated against SH‐SY5Y and K562 cell lines. Compound 3 b [2‐(4‐{2‐methyl‐6‐[(5‐phenylthiazol‐2‐yl)amino]pyrimidin‐4‐yl}piperazin‐1‐yl)ethanol] was found to be the most active inhibitor. 相似文献
10.
Experimental‐numerical research on the seismic performance of URM buildings made of lightweight AAC blocks / Experimentell‐numerische Untersuchung zum seismischen Verhalten von unbewehrten Mauerwerksgebäuden aus Porenbetonblöcken 下载免费PDF全文
Assist. Prof. PhD Andra Penna Professor PhD Guido Magenes Maria Rota Researcher PhD Martina Mandirola MSc Annalisa Rosti MSc 《Mauerwerk》2015,19(2):130-143
Masonry walls constructed with lightweight AAC blocks and thin‐layer mortar meet the increasingly strict requirements of energy efficiency and sustainability. In this sense, they represent an excellent solution for modern buildings, not only for external cladding but also as loadbearing elements. Despite the possible advantages of using lightweight AAC masonry, a specific assessment of its seismic performance is mandatory in order to set design recommendations allowing to reach safety levels consistent with those required for other masonry types complying with EN 1998 standard requirements. A comprehensive study on the seismic performance of unreinforced masonry buildings made of lightweight AAC was carried out in an integrated experimental‐numerical approach. The experimental campaign provided the necessary information to setup a reliable numerical model to be extensively used to assess the seismic performance of a number of prototype AAC masonry buildings with different characteristics, by means of both linear and nonlinear static (pushover) analysis. The results of this systematic numerical assessment were eventually used to draft design recommendations, to set parameters (behaviour factors) to be used in linear analysis and to calibrate rules for simple buildings. 相似文献