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61.
    
User interactions are indispensable for any online network to thrive, especially for BitTorrent‐like and Web real‐time communication‐based distributed online networks that rely on users' collective contributions instead of the help of central servers. User interactions provide fine‐grained information for many applications, such as security enhancement and cooperation promotion. To date, several schemes for estimating user interaction strength in centralized online networks have been proposed. In contrast, we present design, deployment, and analysis of UISE for user interaction strength estimation in distributed online networks. Among the strong points of UISE is that it captures both direct and indirect user interactions, and that it scales with only partial information dissemination. We apply UISE to devise the first distributed scheme for online time estimation and we implement it into Tribler, a distributed online network for media and social applications like file sharing, streaming, and voting. We demonstrate the accuracy and the scalability of UISE with different information dissemination protocols and user behaviors using simulations, emulations, and a real‐world deployment. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   
62.
    
This paper reports on a software understanding field study during the enhancement of large-scale software. The participants were professional software maintenance personnel from industry. The paper reports on the general understanding process, the kinds of actions programmers preferred during the enhancement task, the level of abstraction at which they were working, and role of hypotheses in the enhancement strategies they used. The results of the observations are also interpreted in terms of the information needs of these personnel during the enhancement task. We found that programmers work predominantly at the code and algorithmic levels with differences depending on the stage of the enhancement. They frequently switch between levels of abstraction. The programmers' main concerns are with what software does and how this is accomplished, not why software was built a certain way. These questions guide the work process. There was strong indication that memory (over)load is an issue. This is, of course, related to the size of the software. Information is sought and cross-referenced from a variety of sources from application domain concepts to code-related information, outpacing current maintenance environments' capabilities which are mostly stratified by information sources, making cross-referencing difficult. © 1997 John Wiley & Sons, Ltd.  相似文献   
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64.
    
Olive oil is a common component of Mediterranean dietary habits. Epidemiological studies have shown how the incidence of various diseases, including certain cancers, is relatively low in the Mediterranean basin compared to that of other European or North America countries. Current knowledge indicates that the phenolic fraction of olive oil has antitumor effects. In addition to the ability to be chemopreventive, with its high antioxidant activity, the antitumor effects of olive oil phenols (OO‐phenols) has been studied because of their capacity to inhibit proliferation and promote apoptosis in several tumor cell lines, by diverse mechanisms. This review will summarize and discuss the most recent relevant results on the antitumor effect of OO‐phenols on leukemia tumor cells, colorectal carcinoma cells, and breast cancer (BC) cells. In particular, very recent data will be reported and discussed showing the molecular signaling pathways activated by OO‐phenols in different histopathological BC cell types, suggesting the potential use of OO‐phenols as adjuvant treatment against several subsets of BC. Data summarized here represent a good starting point for more extensive studies for better insight into the molecular mechanisms induced by OO‐phenols and to increase the availability of chemopreventive or therapeutic drugs to fight cancer.  相似文献   
65.
    
We investigated the influence of an in vitro simulated digestion process on the content of the free α‐dicarbonyl compounds most frequently found in food. A Glyoxal (GO), methylglyoxal (MGO), and diacetyl (DA) aqueous standard mixture and 2 brands of balsamic vinegar were analyzed before and after exposure to digestive enzymes. A strong matrix effect required adoption of validated RP‐HPLC‐DAD standard addition methods. The results showed that the digestive enzymes markedly alter the concentrations of the exogenous free α‐dicarbonyl compounds ingested with food; the extent of such changes varied with the α‐dicarbonyl compound itself and the diet components, which determined important but different food matrix effects also during digestion. The data also indicate that digestion can reduce the bioavailability of the toxic α‐dicarbonyl compounds ingested with food. However, no firm conclusions can be drawn about a putative positive influence of digestion on the toxic potential of dietary α‐dicarbonyl compounds, because their reaction in the presence of digestive enzymes likely gives rise to advanced glycation end products, which are involved in the development of chronic diseases.  相似文献   
66.
    
Multi‐junction cells can significantly improve the energy yield of photovoltaic systems over a single‐junction cell. The internal interconnection scheme of the subcells is an important aspect in determining the resulting levelized cost of electricity. For a dual‐junction cell, two approaches are commonly discussed: series‐connected tandem cells with two terminals or independently working subcells in a four‐terminal (4T) tandem device. In this paper, we explore the working principle and the operation modes of a third, rarely discussed option: a three‐terminal (3T) tandem cell using a back‐contacted bottom cell with 3Ts. We use current–voltage measurements of illuminated 3T interdigitated back contact cells and confirm that the front and rear base contacts are at similar quasi‐Fermi level positions, which enables the bottom cell to either efficiently collect surplus carriers, in the case of a current‐limiting or carrier injecting top cell, or inject majority carriers, in the case of a current‐limiting bottom cell. As a result, no current matching is needed. The power output of an idealized 3T bottom cell without resistive effects is independent of the current density applied from the top cell. These characteristics of the 3T bottom cells enable a 3T tandem to operate as efficiently as a 4T tandem, while being compatible with monolithic design and not requiring intermediate grids. We propose a simple equivalent circuit model including additional resistive effects, which describes a real 3T bottom cell and achieves excellent agreement to the experiment. We deduce design guidelines for a 3T bottom cell in different operation regimes.  相似文献   
67.
    
Nucleostemin (NS; a product of the GNL3 gene) is a nucleolar–nucleoplasm shuttling GTPase whose levels are high in stem cells and rapidly decrease upon differentiation. NS levels are also high in several solid and hematological neoplasms, including acute myeloid leukaemia (AML). While a role in telomere maintenance, response to stress stimuli and favoring DNA repair has been proposed in solid cancers, little or no information is available as to the role of nucleostemin in AML. Here, we investigate this issue via a proteomics approach. We use as a model system the OCI-AML 3 cell line harboring a heterozygous mutation at the NPM1 gene, which is the most frequent driver mutation in AML (approximately 30% of total AML cases). We show that NS is highly expressed in this cell line, and, contrary to what has previously been shown in other cancers, that its presence is dispensable for cell growth and viability. However, proteomics analysis of the OCI-AML 3 cell line before and after nucleostemin (NS) silencing showed several effects on different biological functions, as highlighted by ingenuity pathway analysis (IPA). In particular, we report an effect of down-regulating DNA repair through homologous recombination, and we confirmed a higher DNA damage rate in OCI-AML 3 cells when NS is depleted, which considerably increases upon stress induced by the topoisomerase II inhibitor etoposide. The data used are available via ProteomeXchange with the identifier PXD034012.  相似文献   
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69.
    
The substantia nigra is generally considered to show significant cell loss not only in Parkinson’s but also in Alzheimer’s disease, conditions that share several neuropathological traits. An interesting feature of this nucleus is that the pars compacta dopaminergic neurons contain acetylcholinesterase (AChE). Independent of its enzymatic role, this protein is released from pars reticulata dendrites, with effects that have been observed in vitro, ex vivo and in vivo. The part of the molecule responsible for these actions has been identified as a 14-mer peptide, T14, cleaved from the AChE C-terminus and acting at an allosteric site on alpha-7 nicotinic receptors, with consequences implicated in neurodegeneration. Here, we show that free T14 is co-localized with tyrosine hydroxylase in rodent pars compacta neurons. In brains with Alzheimer’s pathology, the T14 immunoreactivity in these neurons increases in density as their number decreases with the progression of the disease. To explore the functional implications of raised T14 levels in the substantia nigra, the effect of exogenous peptide on electrically evoked neuronal activation was tested in rat brain slices using optical imaging with a voltage-sensitive dye (Di-4-ANEPPS). A significant reduction in the activation response was observed; this was blocked by the cyclized variant of T14, NBP14. In contrast, no such effect of the peptide was seen in the striatum, a region lacking the T14 target, alpha-7 receptors. These findings add to the accumulating evidence that T14 is a key signaling molecule in neurodegenerative disorders and that its antagonist NBP14 has therapeutic potential.  相似文献   
70.
    
Breast cancer is the main cause of morbidity and mortality in women worldwide. However, the molecular pathogenesis of breast cancer remains poorly defined due to its heterogeneity. Several studies have reported that G Protein-Coupled Estrogen Receptor 1 (GPER1) plays a crucial role in breast cancer progression, by binding to estrogens or synthetic agonists, like G-1, thus modulating genes involved in diverse biological events, such as cell proliferation, migration, apoptosis, and metastasis. In addition, it has been established that the dysregulation of short sequences of non-coding RNA, named microRNAs (miRNAs), is involved in various pathophysiological conditions, including breast cancer. Recent evidence has indicated that estrogens may regulate miRNA expression and therefore modulate the levels of their target genes, not only through the classical estrogen receptors (ERs), but also activating GPER1 signalling, hence suggesting an alternative molecular pathway involved in breast tumor progression. Here, the current knowledge about GPER1 and miRNA action in breast cancer is recapitulated, reporting recent evidence on the liaison of these two players in triggering breast tumorogenic effects. Elucidating the role of GPER1 and miRNAs in breast cancer might provide new tools for innovative approaches in anti-cancer therapy.  相似文献   
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