全文获取类型
收费全文 | 713篇 |
免费 | 77篇 |
专业分类
电工技术 | 6篇 |
化学工业 | 374篇 |
金属工艺 | 16篇 |
机械仪表 | 13篇 |
建筑科学 | 25篇 |
能源动力 | 9篇 |
轻工业 | 138篇 |
无线电 | 24篇 |
一般工业技术 | 90篇 |
冶金工业 | 23篇 |
原子能技术 | 1篇 |
自动化技术 | 71篇 |
出版年
2024年 | 1篇 |
2023年 | 7篇 |
2022年 | 85篇 |
2021年 | 106篇 |
2020年 | 30篇 |
2019年 | 27篇 |
2018年 | 42篇 |
2017年 | 31篇 |
2016年 | 38篇 |
2015年 | 42篇 |
2014年 | 45篇 |
2013年 | 43篇 |
2012年 | 42篇 |
2011年 | 45篇 |
2010年 | 32篇 |
2009年 | 30篇 |
2008年 | 27篇 |
2007年 | 11篇 |
2006年 | 19篇 |
2005年 | 24篇 |
2004年 | 7篇 |
2003年 | 7篇 |
2002年 | 8篇 |
2001年 | 5篇 |
2000年 | 3篇 |
1999年 | 2篇 |
1998年 | 3篇 |
1997年 | 6篇 |
1996年 | 2篇 |
1995年 | 1篇 |
1994年 | 1篇 |
1993年 | 3篇 |
1991年 | 2篇 |
1987年 | 2篇 |
1986年 | 4篇 |
1981年 | 2篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1975年 | 2篇 |
排序方式: 共有790条查询结果,搜索用时 15 毫秒
1.
Adele Boccuto Filippo Dragoni Francesca Picarazzi Alessia Lai Carla Della Ventura Carla Veo Federica Giammarino Francesco Saladini Gianguglielmo Zehender Maurizio Zazzi Mattia Mori Ilaria Vicenti 《International journal of molecular sciences》2021,22(5)
The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC50) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC50 shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development. 相似文献
2.
3.
Dr. Hui Qiu Richard Caldwell Dr. Lesley Liu-Bujalski Dr. Andreas Goutopoulos Reinaldo Jones Justin Potnick Dr. Brian Sherer Dr. Andrew Bender Dr. Roland Grenningloh Dr. Daigen Xu Dr. Anna Gardberg Dr. Igor Mochalkin Dr. Theresa Johnson Dr. Ariele Viacava Follis Jared Head Dr. Federica Morandi 《ChemMedChem》2019,14(2):217-223
Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon. 相似文献
4.
Davide Barbagallo Angela Caponnetto Cristina Barbagallo Rosalia Battaglia Federica Mirabella Duilia Brex Michele Stella Giuseppe Broggi Roberto Altieri Francesco Certo Rosario Caltabiano Giuseppe Maria Vincenzo Barbagallo Carmelina Daniela Anfuso Gabriella Lupo Marco Ragusa Cinzia Di Pietro Thomas Birkballe Hansen Michele Purrello 《International journal of molecular sciences》2021,22(4)
Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential. 相似文献
5.
The protective properties of epoxy-based organic coatings on mild steel substrates have been studied using the electrochemical impedance spectroscopy (EIS) technique. The effects of coating composition, film thickness and curing temperature on the lifetime of the epoxy coating were investigated. The results obtained indicate that the film composition dramatically affects the rate of corrosion of the metallic substrate. Coatings with low and high content of curing agent exhibit early failure when exposed to an air-saturated 0.5 M aqueous solution of NaCl. Extended lifetimes were observed for samples with a content of the curing agent equal to 8.5% by weight. An increase in lifetime was also observed on increasing the film thickness and the curing temperature. The failure mechanism seems to occur in two steps: the first step is related to water uptake in the film while the second step is related to Cl− ion diffusion through the coating. The results have been interpreted in terms of a model in which the dielectric properties (capacitance and resistance) of the coating depend strongly on the coating composition and are affected by both the water and salt uptake into the film. 相似文献
6.
Super-hydrophobic membranes were manufactured by using two per-fluorinated polymers such as PVDF and Hyflon AD. The combination of controlled structure and supra-molecular chemistry made these membranes ideal interfaces to be used in membrane contactors. 相似文献
7.
Numerical and approximate analytical solutions for salt concentration polarization in hyperfiltration with laminar flow in a flat sheet configuration are presented. The analysis accounts for the variation of the water flux in the longitudinal direction. Approximate solutions were obtained with an integral method which was found to provide good agreement with the numerical solution. The integral method allows one to obtain closed expressions for the productivity Q, the recovery R and the efficiency E of a reverse osmosis system which can be applied relatively quickly in design calculations.In this analysis the physical properties of the solution are taken to be constant. 相似文献
8.
Federica Cucchiella Idiano D’Adamo Massimo Gastaldi S.C. Lenny Koh 《International journal of systems science》2014,45(6):1268-1282
Green supply chain management (GSCM) has emerged as a key approach for enterprises seeking to become environmentally sustainable. This paper aims to evaluate and describe the advantages of a GSCM approach by analysing practices and performance consequences in the battery recycling sector. It seeks to integrate works in supply chain management (SCM), environmental management, performance management and real option (RO) theory into one framework. In particular, life cycle assessment (LCA) is applied to evaluate the environmental impact of a battery recycling plant project, and life cycle costing (LCC) is applied to evaluate its economic impact. Firms, also understanding the relevance of GSCM, have often avoided applying the green principles because of the elevated costs that such management involved. Such costs could also seem superior to the potential advantages since standard performance measurement systems are internally and business focused; for these reasons, we consider all the possible value deriving also by uncertainty associated to a green project using the RO theory. This work is one of the few and pioneering efforts to investigate GSCM practices in the battery recycling sector. 相似文献
9.
An experimental study was carried out on the ultrafiltration (UF) of protein-containing solutions under different conditions, as compared with a solution of a linear synthetic polymer. Three different fluidynamic regimes were investigated, namely, unstirred batch system, stirred batch system, and recirculating system. The results obtained substantially agree with the predictions of the gel polarization model. A significant effect of the electrolytes on the UF flux has been observed, which can be attributed to solute–solute interaction. The influence of different UF membranes has also been investigated. 相似文献
10.
M. O. H. Cioffi H. J. C. Voorwald V. Ambrogi T. Monetta F. Bellucci L. Nicolais 《Journal of Materials Engineering and Performance》2003,12(3):279-287
As a followup to previous work, experiments with argon and oxygen Radio Frequency plasma treated polyethylene terepthalate
(PET) exposed to 100 °C after cold plasma treatment were performed. Tensile tests results in monofilaments treated in oxygen
and argon plasma for 5 s, 20 s, 30 s, and 100 s showed a decrease in the average tensile strength compared with the untreated
fibers. It was also observed that the reduction in mechanical strength is more significant for argon plasma and very sensitive
to the treatment time for oxygen plasma. Experimental data obtained from tensile tests in samples thermal exposed to 100 °C
after plasma treatments indicate the same influence of treatment times on mechanical strength, as observed for cold plasma
treated fibers. Furthermore, an increase in tensile strength when compared with the samples unexposed to 100 °C was observed.
Scanning electron microscopy, used to analyze effects of cold plasma treatment on fibers surfaces, indicates differences in
roughness profiles depending on the type of treatment. The distance of roughness interval, Dri, was a parameter introduced to relate the fibers surface condition and average tensile strength. Statistical analysis of
experimental data was performed to explain influences of treatment time, and environmental and temperature effects on mechanical
properties. 相似文献