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51.
    
We discuss the potential benefits, requirements, and implementation challenges of a security-by-design approach in which an integrated development environment plugin assists software developers to write code that complies with secure coding guidelines. We discuss how such a plugin can enable a company's policy-setting security experts and developers to pass their knowledge on to each other more efficiently, and to let developers more effectively put that knowledge into practice. This is achieved by letting the team members develop customized rule sets that formalize coding guidelines and by letting the plugin check the compliance of code being written to those rule sets in real time, similar to an as-you-type spell checker. Upon detected violations, the plugin suggests options to quickly fix them and offers additional information for the developer. We share our experience with proof-of-concept designs and implementations rolled out in multiple companies, and present some future research and development directions.  相似文献   
52.
    
This article presents a data mining methodology for driving-condition monitoring via CAN-bus data that is based on the general data mining process. The approach is applicable to many driving condition problems, and the example of road type classification without the use of location information is investigated. Location information from Global Positioning Satellites and related map data are often not available (for business reasons), or cannot represent the full dynamics of road conditions. In this work, Controller Area Network (CAN)-bus signals are used instead as inputs to models produced by machine learning algorithms. Road type classification is formulated as two related labeling problems: Road Type (A, B, C, and Motorway) and Carriageway Type (Single or Dual). An investigation is presented into preprocessing steps required prior to applying machine learning algorithms, that is, signal selection, feature extraction, and feature selection. The selection methods used include principal components analysis (PCA) and mutual information (MI), which are used to determine the relevance and redundancy of extracted features and are performed in various combinations. Finally, because there is an inherent bias toward certain road and carriageway labelings, the issue of class imbalance in classification is explained and investigated. A system is produced, which is demonstrated to successfully ascertain road type from CAN-bus data, and it is shown that the classification correlates well with input signals such as vehicle speed, steering wheel angle, and suspension height.  相似文献   
53.
54.
    
The effect of 1 sun illumination for 24 h on encapsulated inverted organic photovoltaic devices is studied through a series of electrical and optical characterizations for donor/acceptor polymer solar cells based on poly(dithienogermole‐alt‐thienopyrrolodione)/[6,6]‐phenyl C71 butyric acid methyl ester blends. Power conversion efficiency is significantly reduced after light exposure due to a 45% drop in the device fill factor and a 40% drop in both the open circuit voltage and short circuit current. The decrease in open circuit voltage is attributed to a reduction in the built‐in field in the device due to photodegradation of the ZnO interlayer. The reduction in fill factor and short circuit current is shown to be due to the formation of an extraction barrier for hole collection as a result of photodegradation of the MoOx interlayer. Using a 400 nm long pass filter to block the UV light, device stability is significantly enhanced, resulting in a decrease in power conversion efficiency of less than 5% under the same operation conditions.  相似文献   
55.
    
This paper considers the numerical solution of linear generalized Nash equilibrium problems (LGNEPs). Since many methods for nonlinear problems require the nonsingularity of some second-order derivative, standard convergence conditions are not satisfied in our linear case. We provide new convergence criteria for a potential reduction algorithm (PRA) that allow its application to LGNEPs. Furthermore, we discuss a projected subgradient method (PSM) and a penalty method that exploit some known Nikaido–Isoda function-based constrained and unconstrained optimization reformulations of the LGNEP. Moreover, it is shown that normalized Nash equilibria of an LGNEP can be obtained by solving a single linear program. All proposed algorithms are tested on randomly generated instances of economic market models that are introduced and analysed in this paper and that lead to LGNEPs with shared and with non-shared constraints. It is shown that these problems have some favourable properties that can be exploited to obtain their solutions. With the PRA and in particular with the PSM we are able to compute solutions with satisfying precision even for problems with up 10,000 variables.  相似文献   
56.
    
Trigeminal neuralgia (TN) is a complex orofacial pain syndrome characterized by the paroxysmal onset of pain attacks in the trigeminal distribution. The underlying mechanism for this debilitating condition is still not clearly understood. Decades of basic and clinical evidence support the demyelination hypothesis, where demyelination along the trigeminal afferent pathway is a major driver for TN pathogenesis and pathophysiology. Such pathological demyelination can be triggered by physical compression of the trigeminal ganglion or another primary demyelinating disease, such as multiple sclerosis. Further examination of TN patients and animal models has revealed significant molecular changes, channelopathies, and electrophysiological abnormalities in the affected trigeminal nerve. Interestingly, recent electrophysiological recordings and advanced functional neuroimaging data have shed new light on the global structural changes and the altered connectivity in the central pain-related circuits in TN patients. The current article aims to review the latest findings on the pathophysiology of TN and cross-examining them with the current surgical and pharmacologic management for TN patients. Understanding the underlying biology of TN could help scientists and clinicians to identify novel targets and improve treatments for this complex, debilitating disease.  相似文献   
57.
    
The cornea, an anterior ocular tissue that notably serves to protect the eye from external insults and refract light, requires constant epithelium renewal and efficient healing following injury to maintain ocular homeostasis. Although several key cell populations and molecular pathways implicated in corneal wound healing have already been thoroughly investigated, insufficient/impaired or excessive corneal wound healing remains a major clinical issue in ophthalmology, and new avenues of research are still needed to further improve corneal wound healing. Because of its implication in numerous cellular/tissular homeostatic processes and oxidative stress, there is growing evidence of the role of Hedgehog signaling pathway in physiological and pathological corneal wound healing. Reviewing current scientific evidence, Hedgehog signaling and its effectors participate in corneal wound healing mainly at the level of the corneal and limbal epithelium, where Sonic Hedgehog-mediated signaling promotes limbal stem cell proliferation and corneal epithelial cell proliferation and migration following corneal injury. Hedgehog signaling could also participate in corneal epithelial barrier homeostasis and in pathological corneal healing such as corneal injury-related neovascularization. By gaining a better understanding of the role of this double-edged sword in physiological and pathological corneal wound healing, fascinating new research avenues and therapeutic strategies will undoubtedly emerge.  相似文献   
58.
    
Recent evidence suggests that I2-imidazoline ligands have neuroprotective properties in animal models of neurodegeneration, such as Alzheimer’s disease (AD). We recently demonstrated that the I2-ligand BU224 reversed memory impairments in AD transgenic mice and this effect was not because of reductions in amyloid-β (Aβ) deposition. In this study, our aim was to determine the therapeutic potential of the powerful analgesic I2-imidazoline ligand CR4056 in the 5xFAD model of AD, since this ligand has been proven to be safely tolerated in humans. Sub-chronic oral administration of CR4056 (30 mg/kg for 10 days) led to an improvement in recognition memory in 6-month-old 5xFAD mice, but not in wild-type littermates, without affecting Aβ levels or deposition. Our results also revealed a change in the profile of microglia by CR4056, resulting in a suppression of pro-inflammatory activated microglia, but increased the density of astrocytes and the expression of ApoE, which is mainly produced by these glial cells. In addition, CR4056 restored fibrinogen extravasation, affecting the distribution of markers of astrocytic end feet in blood vessels. Therefore, these results suggest that CR4056 protects against Aβ-mediated neuroinflammation and vascular damage, and offers therapeutic potential at any stage of AD.  相似文献   
59.
    
Most in vitro iron mobilization studies from ferritin have been performed in aqueous buffered solutions using a variety of reducing substances. The kinetics of iron mobilization from ferritin in a medium that resembles the complex milieu of cells could dramatically differ from those in aqueous solutions, and to our knowledge, no such studies have been performed. Here, we have studied the kinetics of iron release from ferritin in fresh yeast cell lysates and examined the effect of cellular metabolites on this process. Our results show that iron release from ferritin in buffer is extremely slow compared to cell lysate under identical experimental conditions, suggesting that certain cellular metabolites present in yeast cell lysate facilitate the reductive release of ferric iron from the ferritin core. Using filtration membranes with different molecular weight cut-offs (3, 10, 30, 50, and 100 kDa), we demonstrate that a cellular component >50 kDa is implicated in the reductive release of iron. When the cell lysate was washed three times with buffer, or when NADPH was omitted from the solution, a dramatic decrease in iron mobilization rates was observed. The addition of physiological concentrations of free flavins, such as FMN, FAD, and riboflavin showed about a two-fold increase in the amount of released iron. Notably, all iron release kinetics occurred while the solution oxygen level was still high. Altogether, our results indicate that in addition to ferritin proteolysis, there exists an auxiliary iron reductive mechanism that involves long-range electron transfer reactions facilitated by the ferritin shell. The physiological implications of such iron reductive mechanisms are discussed.  相似文献   
60.
2,4-Thiazolidinedione (TZD) is a privileged and highly utilised scaffold for the development of pharmaceutically active compounds. This sulfur-containing heterocycle is a versatile pharmacophore that confers a diverse range of pharmacological activities. TZD has been shown to exhibit biological action towards a vast range of targets interesting to medicinal chemists. In this review, we attempt to provide insight into both the historical conventional and the use of novel methodologies to synthesise the TZD core framework. Further to this, synthetic procedures utilised to substitute the TZD molecule at the activated methylene C5 and N3 position are reviewed. Finally, research into developing clinical agents, which act as modulators of peroxisome proliferator-activated receptors gamma (PPARγ), protein tyrosine phosphatase 1B (PTP1B) and aldose reductase 2 (ALR2), are discussed. These are the three most targeted receptors for the treatment of diabetes mellitus (DM).  相似文献   
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