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As part of our ongoing studies on the potential pathophysiological role of serine/threonine phosphatases (PP) in the mammalian heart, we have generated transgenic mice with cardiac muscle cell-specific overexpression of PP2Acα (PP2A) and PP5 (PP5). For further studies we crossbred PP2A and PP5 mice to obtain PP2AxPP5 double transgenic mice (PP2AxPP5, DT) and compared them with littermate wild-type mice (WT) serving as a control. The mortality of DT mice was greatly enhanced vs. other genotypes. Cardiac fibrosis was noted histologically and mRNA levels of collagen 1α, collagen 3α and fibronectin 1 were augmented in DT. DT and PP2A mice exhibited an increase in relative heart weight. The ejection fraction (EF) was reduced in PP2A and DT but while the EF of PP2A was nearly normalized after β-adrenergic stimulation by isoproterenol, it was almost unchanged in DT. Moreover, left atrial preparations from DT were less sensitive to isoproterenol treatment both under normoxic conditions and after hypoxia. In addition, levels of the hypertrophy markers atrial natriuretic peptide and B-type natriuretic peptide as well as the inflammation markers interleukin 6 and nuclear factor kappa B were increased in DT. PP2A enzyme activity was enhanced in PP2A vs. WT but similar to DT. This was accompanied by a reduced phosphorylation state of phospholamban at serine-16. Fittingly, the relaxation times in left atria from DT were prolonged. In summary, cardiac co-overexpression of PP2A and PP5 were detrimental to animal survival and cardiac function, and the mechanism may involve dephosphorylation of important regulatory proteins but also fibrosis and inflammation.  相似文献   
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Multi‐user systems (MUS) for electrification of rural villages have specific advantages compared with individual systems (SHS). However, as MUS serve multiple consumers, shared energy use presents a challenging problem to the communities. Despite the increased performance of MUS over SHS, they still produce a limited amount of available energy, and users cannot consume as much electricity as they wish without considering the needs of the other users. This means that energy distribution among village residents has to be organised and energy consumption has to be controlled. There are different ways to achieve energy distribution. One possibility is to leave it to the users themselves to organise rational energy use according to their needs and daily routines. For the development of a self‐managed scheme, knowledge is required not only of the users' total energy consumption, but also of their individual energy use patterns. With knowledge of the community's energy consumption habits, rules for adequate energy use can be developed more accurately. The present study describes community energy management in a Cuban village using a central photovoltaic installation. Applying different methods, data were collected in order to identify individual energy use patterns and to investigate how villagers distribute energy and what rules of use are in effect. We wanted to find out whether their energy management leads to well‐adapted energy use patterns and reasonable system performance. The results show that the village residents have developed rules and agreements for coordination of their energy use that have led to good adaptation to the dynamics of energy production. Copyright © 2006 John Wiley & Sons, Ltd.  相似文献   
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Damage calculation at a prestressed concrete tower for a Wind Energy Converter subjected to multi‐stage fatigue loading The application of a linear damage accumulation law devised by Palmgren and Miner for dimensioning constructions of Wind Energy Converters could lead to very unsafe or uneconomical calculation results. The real high non‐linear fatigue behaviour of concrete is not considered sufficiently by a simplified linear damage model. Additionally effects of different orders of load cycles to the resulting fatigue life are not represented as well. Based on a mechanical damage model available in literature a proceeding is established to determine the stiffness and damage evolution in concrete under multi‐stage fatigue loading. This extended damage approach is associated with the elastic‐plastic material model for concrete providing in the FE‐Program ABAQUS and subsequently a numerical investigation at a prestressed concrete tower for a multi‐megawatt wind turbine is performed. The results of the numerical simulation indicate obviously the influence of the order of load cycles to the fatigue life and that due to alterations of stress distributions a significant lower fatigue damage state occurs compared with calculation results without stress alterations.  相似文献   
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Joachim Naumann 《Stahlbau》2006,75(10):779-785
Current developments of road bridges in Germany. In connection with the major tasks after the reunification of Germany for the creation and improvement of the traffic infrastructure in the East German States an exceptionally large number of bridges and other transportation structures have newly been built or have been rehabilitated in connection with the widening of Freeways. The engineers in charge took up this opportunity quickly to initiate new technical developments and to realize innovative solutions. This is true for reinforced and pre‐stressed concrete bridges as well as for steel composite bridges in particular. Many good examples for current bridge design were built especially for the Freeways A71/A73 across the Thuringia Forest and for the A4 around Dresden. At the same time the German national codes were replaced by the modern European Eurocodes so that the state‐of‐the‐art of bridge design in Germany today is compatible with international standards.  相似文献   
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Analysis for improved energy consumption calculation of construction sites. The energy demand of construction sites depends on a variety of factors which are characterized by a wide range and low predictability. Looking at the increasing energy costs, the need for developing an efficient energy controlling system will be required. Hereby, the interaction between construction processes and technical properties of the construction equipment marks a main challenge for the controlling of the energy costs. With the intention to make new technologies accessible for a moderate as well as cost efficient use of energy resources on construction sites, the construction company Max Bögl and the Chair of Construction Engineering and Management at the Bauhaus University Weimar developed concepts and methods, which make possible the structured collection of relevant energy‐consuming processes. Finally a Software Application has been developed, with which further development and approvement of energy management systems of construction sites have been made possible.  相似文献   
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Background

Biomonitoring is used in exposure and risk assessments to reduce uncertainties along the source-to-outcome continuum. Specifically, biomarkers can help identify exposure sources, routes, and distributions, and reflect kinetic and dynamic processes following exposure events. A variety of computational models now utilize biomarkers to better understand exposures at the population, individual, and sub-individual (target) levels. However, guidance is needed to clarify biomonitoring use given available measurements and models.

Objective

This article presents a biomonitoring research framework designed to improve biomarker use and interpretation in support of exposure and risk assessments.

Discussion

The biomonitoring research framework is based on a modified source-to-outcome continuum. Five tiers of biomonitoring analyses are included in the framework, beginning with simple cross-sectional and longitudinal analyses, and ending with complex analyses using various empirical and mechanistic models. Measurements and model requirements of each tier are given, as well as considerations to enhance analyses. Simple theoretical examples are also given to demonstrate applications of the framework for observational exposure studies.

Conclusion

This biomonitoring framework can be used as a guide for interpreting existing biomarker data, designing new studies to answer specific exposure- and risk-based questions, and integrating knowledge across scientific disciplines to better address human health risks.  相似文献   
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