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101.
The layer removal analysis of residual stress distribution is examined for mouldings which contain depth-varying Young's modulus. The approach is to compute the stress distribution which would be derived from the layer removal procedure if the assumption is made that the Young's modulus is uniform, and to compare it with the actual stress distribution. For this analysis a parabolic stress distribution is assumed to be present, and computed distributions are obtained for two cases, (i) in which the modulus varies linearly from the surface to the centre of the moulding and (ii) in which the modulus has a constant value near to the surface (skin) then changes suddenly to another constant value in the interior (core). The general features of the computed profiles are compared with experimental layer removal analyses conducted on injection-moulded specimens and the extent to which non-uniform modulus influences the results of such studies is discussed.  相似文献   
102.
Atomic Energy of Canada Limited and Ontario Hydro are conducting a research program to assess the environmental impact and safety of the concept of disposal of nuclear fuel waste in an underground vault in plutonic rock of the Canadian Shield. The Vault Sealing Program, one of the components of the Nuclear Fuel Waste Management Program, is concerned with the development of materials specifications and emplacement procedures for backfilling the vault. Backfilling materials would surround the nuclear waste containers and fill all vault openings to minimize leaching and movement of radionuclides. This paper presents the procedure followed to select candidate backfill materials, the integration of mathematical modelling studies and physical testing for the definition of materials specifications, and the principal elements of the recommended handling and emplacement systems.  相似文献   
103.
Summary This paper deals with discounted Markov decision processes, Markov with respect to a finite statespaceI, where for eachiI, and each decision epocht, there is a finite action space K(i, t). The paper is concerned with problems which are formulated in terms of the discounted rewards in several ways. In order to ensure that optimal, or near optimal, policies are obtained, the state spaceI is extended to augmented state-spaces A(n), or A(), including the accumulated discounted rewards. Specimen problems are formulated and some computational aspects examined.
Zusammenfassung Es werden diskontierte Markovsche Entscheidungsprozesse behandelt mit endlichem Zustandsraum I, wobei die Mengen der zulässigen Entscheidungen K(i, t) vom Zustandi I und vom Zeitpunktt abhängen können. Es werden verschiedene Zielfunktionen betrachtet, die jeweils als Funktion des diskontierten Gesamtgewinns (nicht dessen Erwartungswerts) formuliert werden. Um optimale oder fast-optimale Politiken zu erhalten ohne die gesamte Vorgeschichte zu registrieren, wird der Zustandsraum um die akkumulierten diskontierten Auszahlungen erweitert. Eine Auswahl solcher Probleme wird exemplarisch diskutiert einschließlich einiger Aspekte der numerischen Behandlung.
  相似文献   
104.
Summary We integrate two numerical procedures for solving the average reward Markov decision process (MDP), standard successive approximations and modified policy iteration with reward revision. Reward revision is the process of revising the reward structure of a second, more computationally desirable MDP so as to produce, in the limit, an optimality equation having a fixed point identical to that associated with the original MDP. A numerical study indicates that for MDP's having a non-sparse transition structure with a small number of relatively large entries per row, the addition of reward revision can have significant computational benefits.
Zusammenfassung Zur Lösung Markovscher Entscheidungsprozesse (MDP) mit Durchschnitts-Kriterium werden zwei numerische Verfahren, nämlich sukzessive Approximation und modifizierte Politik-Iteration, mit einer Transformation, der sogenannten 'Reward-Revision, kombiniert. Bei dieser Transformation werden die Übergangswahrscheinlichkeiten so abgeändert (ausgedünnt), daß das neue Modell sich numerisch günstiger verhält. Dazu müssen die einstufigen Erträge so revidiert werden, daß die Optimalitäts-Gleichung des neuen Modells im Limes mit der des ursprünglichen übereinstimmt. Numerische Untersuchungen zeigen, daß für MDP mit stark besetzten Übergangsmatrizen, bei denen nur an wenigen Stellen je Zeile große Werte stehen, die Anwendung von 'Reward Revision zu wesentlichen Einsparungen an Rechenaufwand führen kann.


Research supported by NSF Grant ECS-8319355  相似文献   
105.
106.
Systemic Acquired Resistance (SAR) improves immunity of plant systemic tissue after local exposure to a pathogen. Guard cells that form stomatal pores on leaf surfaces recognize bacterial pathogens via pattern recognition receptors, such as Flagellin Sensitive 2 (FLS2). However, how SAR affects stomatal immunity is not known. In this study, we aim to reveal molecular mechanisms underlying the guard cell response to SAR using multi-omics of proteins, metabolites and lipids. Arabidopsis plants previously exposed to pathogenic bacteria Pseudomonas syringae pv. tomato DC3000 (Pst) exhibit an altered stomatal response compared to control plants when they are later exposed to the bacteria. Reduced stomatal apertures of SAR primed plants lead to decreased number of bacteria in leaves. Multi-omics has revealed molecular components of SAR response specific to guard cells functions, including potential roles of reactive oxygen species (ROS) and fatty acid signaling. Our results show an increase in palmitic acid and its derivative in the primed guard cells. Palmitic acid may play a role as an activator of FLS2, which initiates stomatal immune response. Improved understanding of how SAR signals affect stomatal immunity can aid biotechnology and marker-based breeding of crops for enhanced disease resistance.  相似文献   
107.
Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants produced by incomplete combustion of organic matter. They induce their own metabolism by upregulating xenobiotic-metabolizing enzymes such as cytochrome P450 monooxygenase 1A1 (CYP1A1) by activating the aryl hydrocarbon receptor (AHR). However, previous studies showed that individual PAHs may also interact with the constitutive androstane receptor (CAR). Here, we studied ten PAHs, different in carcinogenicity classification, for their potential to activate AHR- and CAR-dependent luciferase reporter genes in human liver cells. The majority of investigated PAHs activated AHR, while non-carcinogenic PAHs tended to activate CAR. We further characterized gene expression, protein abundancies and activities of the AHR targets CYP1A1 and 1A2, and the CAR target CYP2B6 in human HepaRG hepatoma cells. Enzyme induction patterns strongly resembled the profiles obtained at the receptor level, with AHR-activating PAHs inducing CYP1A1/1A2 and CAR-activating PAHs inducing CYP2B6. In summary, this study provides evidence that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes. Furthermore, we found that an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smaller PAHs activated CAR but showed no DNA-damaging potential.  相似文献   
108.
Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca2+ content and lower frequency of spontaneous Ca2+ signals in SGCE MSNs. Blocking of voltage-gated Ca2+ channels by verapamil was less efficient in suppressing KCl-induced Ca2+ peaks of SGCE MSNs. Ca2+ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca2+ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.  相似文献   
109.
Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.  相似文献   
110.
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