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排序方式: 共有1676条查询结果,搜索用时 15 毫秒
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Fabiana Piscitelli Roberto Coccurello Antonio Totaro Alessandro Leuti Giacomo Giacovazzo Roberta Verde Emanuela Rossi Michele Podaliri Vulpiani Nicola Ferri Roberto Giacominelli Stuffler Vincenzo Di Marzo Sergio Oddi Tiziana Bisogno Mauro Maccarrone 《European Journal of Lipid Science and Technology》2019,121(10)
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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
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The size effects on the mean values of the mechanical properties of condensed matter and on the related variances are analysed by means of a unified approach based on the multiscale character of energy dissipation. In particular, the scaling law for fragmentation energy density is obtained taking into account the self-similarity of fragments. It is based on a generalization of the three classical comminution laws that has been performed to evaluate the energy dissipation, computing volume and surface area of the particles for one- two- and three-dimensional fragmented objects. The result is general and can be applied to different fractal energy dissipation mechanisms, e.g., plasticity. Based on this approach, the scaling laws for mean and standard deviation values of the main mechanical properties of materials can be derived, like Young's and shear elastic moduli, ultimate normal and shear stresses and strains, fracture energy and toughness. 相似文献
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Statistical machine translation systems are usually trained on large amounts of bilingual text (used to learn a translation
model), and also large amounts of monolingual text in the target language (used to train a language model). In this article
we explore the use of semi-supervised model adaptation methods for the effective use of monolingual data from the source language
in order to improve translation quality. We propose several algorithms with this aim, and present the strengths and weaknesses
of each one. We present detailed experimental evaluations on the French–English EuroParl data set and on data from the NIST
Chinese–English large-data track. We show a significant improvement in translation quality on both tasks. 相似文献
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The interactivity effect in multimedia learning 总被引:4,自引:1,他引:3
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In comparing our calculated exciton energies with those obtained from pseudopotential calculations (Ref. 27) and from a previous
tight binding calculation (Ref. 30), we stated that the differences between the three semi-empirical calculations arise because
of different treatment of the nanocrystal surfaces. This appears not to be correct. Subsequent calculations with variable
Si-H parameters have shown that the band gap is actually rather insensitive to the actual value of these. Instead, the important
feature appears to be the overall quality of the bulk band structure parameterization. References 27 and 30 use more extensive
and higher quality empirical parameterizations for bulk Si than the sp3s∗ model used by us. Repeating our time dependent calculations with an improved sp3d5 parameterization results in similar values to those of Refs. 27 and 30 for the exciton energies.1 The agreement of the sp3s∗ values with experimental photoluminescence energies (Fig. 7) cannot, therefore, be regarded as well understood at this
time.1,2 相似文献
10.
Generalizations and unification of the celebrated Paris’ and Wöhler’s laws for fatigue crack propagation are derived by applying the recently developed quantized (or finite) fracture mechanics. In particular, three generalized Paris’, Wöhler’s or unified laws are proposed and compared, demonstrating their applicability for predicting the life time of structures containing from small (the Wöhler’s regime) to large (the Paris’ regime) propagating fatigue cracks. 相似文献