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141.
This study discusses microstructure evolution, diffusion behavior and bonding strength of a couple comprising of an iron aluminium alloy (Fe–Al) and high carbon-steel (FeCMn) during diffusion bonding. A columnar microstructure evolves from the joint interface toward FeCMn and disappears in couples bonded for a long period. Aluminium diffusion from Fe–Al to FeCMn and columnar microstructure evolution are retarded as compared to a couple consisting of an Fe–Al and ferrite steel. The carbide in the FeCMn impedes the aluminium diffusion and retards the columnar grain evolution. When the carbide is dissolved in the ferrite during the aluminium diffsuion from Fe–Al, coarse grains evolve due to the coalescence of the columnar grains and a high-bonding strength is obtained. The hardness variation is minimum in the FeCMn of a couple bonded for a short period, which is explained by the microstructural changes in the columnar grain evolution and carbide dissociation.  相似文献   
142.
The cathodic performance of some metal sulfide electrodes has been investigated in a liquid ammonia solution of NH4SCN. In dry liquid ammonia, the  相似文献   
143.
144.
    
The ceramide transport protein (CERT) delivers ceramide from the endoplasmic reticulum (ER) to the Golgi apparatus, where ceramide is converted to sphingomyelin (SM). The function of CERT is regulated in two distinct phosphorylation-dependent events: multiple phosphorylations in a serine-repeat motif (SRM) and phosphorylation of serine 315 residue (S315). Pharmacological inhibition of SM biosynthesis results in an increase in SRM-dephosphorylated CERT, which serves as an activated form, and an enhanced phosphorylation of S315, which augments the binding of CERT to ER-resident VAMP-associated protein (VAP), inducing the full activation of CERT to operate at the ER–Golgi membrane contact sites (MCSs). However, it remains unclear whether the two phosphorylation-dependent regulatory events always occur coordinately. Here, we describe that hyperosmotic stress induces S315 phosphorylation without affecting the SRM-phosphorylation state. Under hyperosmotic conditions, the binding of CERT with VAP-A is enhanced in an S315 phosphorylation-dependent manner, and this increased binding occurs throughout the ER rather than restrictedly at the ER–Golgi MCSs. Moreover, we found that de novo synthesis of SM with very-long acyl chains preferentially increases via a CERT-independent mechanism under hyperosmotic-stressed cells, providing an insight into a CERT-independent ceramide transport pathway for de novo synthesis of SM.  相似文献   
145.
    
Lipid transfer proteins (LTPs) are recognized as key players in the inter-organelle trafficking of lipids and are rapidly gaining attention as a novel molecular target for medicinal products. In mammalian cells, ceramide is newly synthesized in the endoplasmic reticulum (ER) and converted to sphingomyelin in the trans-Golgi regions. The ceramide transport protein CERT, a typical LTP, mediates the ER-to-Golgi transport of ceramide at an ER-distal Golgi membrane contact zone. About 20 years ago, a potent inhibitor of CERT, named (1R,3S)-HPA-12, was found by coincidence among ceramide analogs. Since then, various ceramide-resembling compounds have been found to act as CERT inhibitors. Nevertheless, the inevitable issue remains that natural ligand-mimetic compounds might directly bind both to the desired target and to various undesired targets that share the same natural ligand. To resolve this issue, a ceramide-unrelated compound named E16A, or (1S,2R)-HPCB-5, that potently inhibits the function of CERT has recently been developed, employing a series of in silico docking simulations, efficient chemical synthesis, quantitative affinity analysis, protein–ligand co-crystallography, and various in vivo assays. (1R,3S)-HPA-12 and E16A together provide a robust tool to discriminate on-target effects on CERT from off-target effects. This short review article will describe the history of the development of (1R,3S)-HPA-12 and E16A, summarize other CERT inhibitors, and discuss their possible applications.  相似文献   
146.
    
Superoxide dismutase (SOD) is a major antioxidant enzyme for superoxide removal, and cytoplasmic SOD (SOD1) is expressed as a predominant isoform in all cells. We previously reported that renal SOD1 deficiency accelerates the progression of diabetic nephropathy (DN) via increasing renal oxidative stress. To evaluate whether the degree of SOD1 expression determines regeneration capacity and sarcopenic phenotypes of skeletal muscles under incipient and advanced DN conditions, we investigated the alterations of SOD1 expression, oxidative stress marker, inflammation, fibrosis, and regeneration capacity in cardiotoxin (CTX)-injured tibialis anterior (TA) muscles of two Akita diabetic mouse models with different susceptibility to DN, DN-resistant C57BL/6-Ins2Akita and DN-prone KK/Ta-Ins2Akita mice. Here, we report that KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, exhibit delayed muscle regeneration after CTX injection, as demonstrated by the finding indicating significantly smaller average cross-sectional areas of regenerating TA muscle myofibers relative to KK/Ta-wild-type mice. Furthermore, we observed markedly reduced SOD1 expression in CTX-injected TA muscles of KK/Ta-Ins2Akita mice, but not C57BL/6-Ins2Akita mice, along with increased inflammatory cell infiltration, prominent fibrosis and superoxide overproduction. Our study provides the first evidence that SOD1 reduction and the following superoxide overproduction delay skeletal muscle regeneration through induction of overt inflammation and fibrosis in a mouse model of progressive DN.  相似文献   
147.
148.
    
Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) and its triggering of interferon-β production. Because MAP2K3 seems to play a role in antiviral immunity against HAV infection, it is a promising target for drug development. The inhibition of MAP2K3 may also prevent HAV patients from developing a severe hepatitis A infection.  相似文献   
149.
In magnetized plasmas, the presence of a significant number of energetic electrons has been observed but quantitative characteristics of these electrons are proving difficult to investigate. A Langmuir probe offers a means to provide quantitative measurement of these energetic electrons that takes into account electron emissions (secondary electron emission and electron reflection) from the probe tips and sheath expansion around the probe tips caused by a considerable negative potential. In this paper, these effects are experimentally confirmed and an analytical means to measure energetic electron characteristics are proposed. An analysis of plasmas produced by a high frequency wave is then applied leading to the successful detection of an asymmetric flow of energetic electrons. The estimated electron temperature and current density were approximately 4-5 keV and 2-3 kA/m(2).  相似文献   
150.
The first neutral beam (NB) injection system of the Korea Superconducting Tokamak Advanced Research (KSTAR) tokamak was partially completed in 2010 with only 1∕3 of its full design capability, and NB heating experiments were carried out during the 2010 KSTAR operation campaign. The ion source is composed of a JAEA bucket plasma generator and a KAERI large multi-aperture accelerator assembly, which is designed to deliver a 1.5 MW, NB power of deuterium at 95 keV. Before the beam injection experiments, discharge, and beam extraction characteristics of the ion source were investigated. The ion source has good beam optics in a broad range of beam perveance. The optimum perveance is 1.1-1.3 μP, and the minimum beam divergence angle measured by the Doppler shift spectroscopy is 0.8°. The ion species ratio is D(+):D(2)(+):D(3)(+) = 75:20:5 at beam current density of 85 mA/cm(2). The arc efficiency is more than 1.0 A∕kW. In the 2010 KSTAR campaign, a deuterium NB power of 0.7-1.5 MW was successfully injected into the KSTAR plasma with a beam energy of 70-90 keV. L-H transitions were observed within a wide range of beam powers relative to a threshold value. The edge pedestal formation in the T(i) and T(e) profiles was verified through CES and electron cyclotron emission diagnostics. In every deuterium NB injection, a burst of D-D neutrons was recorded, and increases in the ion temperature and plasma stored energy were found.  相似文献   
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