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P Burlet C Huber S Bertrandy MA Ludosky I Zwaenepoel O Clermont J Roume AL Delezoide J Cartaud A Munnich S Lefebvre 《Canadian Metallurgical Quarterly》1998,7(12):1927-1933
Spinal muscular atrophy (SMA) is a common autosomal recessive neuromuscular disorder characterized by degeneration of motor neurons of the spinal cord and muscular atrophy. SMA is caused by alterations to the survival of motor neuron (SMN) gene, the function of which has hitherto been unclear. Here, we present immunoblot analyses showing that normal SMN protein expression undergoes a marked decay in the postnatal period compared with fetal development. Morphological and immunohistochemical analyses of the SMN protein in human fetal tissues showed a general distribution in the cytoplasm, except in muscle cells, where SMN protein was immunolocalized to large cytoplasmic dot-like structures and was tightly associated with membrane-free heavy sedimenting complexes. These cytoplasmic structures were similar in size to gem. The SMN protein was markedly deficient in tissues derived from type I SMA fetuses, including skeletal muscles and, as previously shown, spinal cord. While our data do not help decide whether SMA results from impaired SMN expression in spinal cord, skeletal muscle or both, they suggest a requirement for SMN protein during embryo-fetal development. 相似文献
43.
Villin 14T, a representative domain from the actin severing and bundling protein villin, binds calcium ions and actin monomers. To begin to understand the contributions of mobility to the villin-calcium and villin-actin interactions, relaxation rates for magnetization involving the amide nitrogens and protons have been measured for 15N-labeled villin 14T in solution. Although we have measured the complete set of rates required for a full spectral density map, difficulties in the accurate measurement of relaxation rates for antiphase coherence and two-spin order led us to consider a reduced mapping formalism. From the reduced spectral density map, a model-free analysis, or directly from the measured Nx,y relaxation rates, local variations in mobility along the backbone of villin 14T have been revealed. Fast motions are evident not only at the amino and carboxyl termini but also in the turn between strands beta 4 and beta 5 of the central beta-sheet and in the turn between helix alpha 3 and strand beta 7. Slower motions are suggested for the turn between strands beta 2 and beta 3. Motions on the microsecond to millisecond time scale have been probed directly by examining the dependence of the proton transverse relaxation rate on the spin-locking field strength. Leu11 shows a strong dependence on field strength, implying conformational exchange with a time constant of 125 +/- 69 microseconds. The backbone at the actin-binding interface appears to be rather rigid. 相似文献
44.
Alexandre N. Tuch Eva E. Presslaber Markus Stöcklin Klaus Opwis Javier A. Bargas-Avila 《International journal of human-computer studies》2012,70(11):794-811
This paper experimentally investigates the role of visual complexity (VC) and prototypicality (PT) as design factors of websites, shaping users' first impressions by means of two studies. In the first study, 119 screenshots of real websites varying in VC (low vs. medium vs. high) and PT (low vs. high) were rated on perceived aesthetics. Screenshot presentation time was varied as a between-subject factor (50 ms vs. 500 ms vs. 1000 ms). Results reveal that VC and PT affect participants' aesthetics ratings within the first 50 ms of exposure. In the second study presentation times were shortened to 17, 33 and 50 ms. Results suggest that VC and PT affect aesthetic perception even within 17 ms, though the effect of PT is less pronounced than the one of VC. With increasing presentation time the effect of PT becomes as influential as the VC effect. This supports the reasoning of the information-processing stage model of aesthetic processing (Leder et al., 2004), where VC is processed at an earlier stage than PT. Overall, websites with low VC and high PT were perceived as highly appealing. 相似文献
45.
Johansson T. Abbasi M. Huber R.J. Normann R.A. 《IEEE transactions on bio-medical engineering》1992,39(12):1292-1297
A three-dimensional architecture for a photosensing array has been developed. This silicon based architecture consists of a 10 x 10 array of photosensors with 80 microns diameter, through chip interconnects to the back side of a 500 microns thick silicon wafer. Each photosensor consists of a 300 x 300 microns pn-junction photodiode. The following processes were used to create this photosensing architecture: 1) thermomigration of aluminum pads through an n-type silicon wafer; 2) creation of pn-junction photosensors on one side of the wafer; and 3) creation of aluminum pad ohmic contacts to the thermomigrated, through chip interconnects and the substrate on the back side of the wafer. The electrical and optical characteristics of the three-dimensional architecture indicates that it should be well suited as a photosensing framework around which a "silicon retina" could be built. 相似文献
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Elvira S. Sandin Julica Folberth Helge Müller-Fielitz Claus U. Pietrzik Elisabeth Herold Thomas E. Willnow Paul T. Pfluger Ruben Nogueiras Vincent Prevot Thomas Krey Markus Schwaninger 《International journal of molecular sciences》2021,22(9)
The mechanisms underlying the transport of leptin into the brain are still largely unclear. While the leptin receptor has been implicated in the transport process, recent evidence has suggested an additional role of LRP2 (megalin). To evaluate the function of LRP2 for leptin transport across the blood-brain barrier (BBB), we developed a novel leptin-luciferase fusion protein (pLG), which stimulated leptin signaling and was transported in an in vitro BBB model based on porcine endothelial cells. The LRP inhibitor RAP did not affect leptin transport, arguing against a role of LRP2. In line with this, the selective deletion of LRP2 in brain endothelial cells and epithelial cells of the choroid plexus did not influence bodyweight, body composition, food intake, or energy expenditure of mice. These findings suggest that LRP2 at the BBB is not involved in the transport of leptin into the brain, nor in the development of obesity as has previously been described. 相似文献
50.
Iris Ribitsch Andrea Bileck Alexander D. Aldoshin Maciej M. Kadua Rupert L. Mayer Monika Egerbacher Simone Gabner Ulrike Auer Sinan Gültekin Johann Huber David P. Kreil Christopher Gerner Florien Jenner 《International journal of molecular sciences》2021,22(11)
Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies. 相似文献