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41.
    
Pancreatic ductal adenocarcinoma (PDAC), a highly aggressive malignancy with a poor prognosis is usually detected at the advanced stage of the disease. The only US Food and Drug Administration-approved biomarker that is available for PDAC, CA 19-9, is most useful in monitoring treatment response among PDAC patients rather than for early detection. Moreover, when CA 19-9 is solely used for diagnostic purposes, it has only a recorded sensitivity of 79% and specificity of 82% in symptomatic individuals. Therefore, there is an urgent need to identify reliable biomarkers for diagnosis (specifically for the early diagnosis), ascertain prognosis as well as to monitor treatment response and tumour recurrence of PDAC. In recent years, proteomic technologies are growing exponentially at an accelerated rate for a wide range of applications in cancer research. In this review, we discussed the current status of biomarker research for PDAC using various proteomic technologies. This review will explore the potential perspective for understanding and identifying the unique alterations in protein expressions that could prove beneficial in discovering new robust biomarkers to detect PDAC at an early stage, ascertain prognosis of patients with the disease in addition to monitoring treatment response and tumour recurrence of patients.  相似文献   
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A series of chemical optimizations, which was guided by in vitro affinity at histamine H3 receptor (H3R), modulation of lipophilicity, ADME properties and preclinical efficacy resulted in the identification of 1-[2-(1-cyclobutylpiperidin-4-yloxy)-6,7-dihydro-4H-thiazolo[5,4-c]pyridin-5-yl]propan-1-one ( 45 e ) as a potent and selective (Ki=4.0 nM) H3R inverse agonist. Dipsogenia induced by (R)-α-methylhistamine was dose dependently antagonized by 45 e , confirming its functional antagonism at H3R. It is devoid of hERG and phospholipidosis issues. Compound 45 e has adequate oral exposures and favorable half-life in both rats and dogs. It has demonstrated high receptor occupancy (ED80=0.22 mg/kg) and robust efficacy in object recognition task and, dose dependently increased acetylcholine levels in brain. The sub-therapeutic doses of 45 e in combination with donepezil significantly increased acetylcholine levels. The potent affinity, selectivity, in vivo efficacy and drug like properties together with safety, warrant for further development of this molecule for potential treatment of cognitive disorders associated with Alzheimer's disease.  相似文献   
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The computer analysis of steel braced barrel vaults is presented. This analysis is compared with the approximate method of analysis suggested by Baer. The drawbacks of Baer's method are discussed. The behaviour of these frames due to the effect of laterals, edge trusses and different types of bracing systems is predicted. Based on this parametric study an economic system of braced barrel vault is suggested for practical applications.  相似文献   
46.
ABSTRACT

Increasing concerns over the starting of induction motors with high starting torque requirements have prompted engineers to seek methods of starting with full voltage and switched capacitors. This method provides ample acceleration torque with minimum voltage disturbances on the main bus. A highly reliable microprocessor-based starter with high performance has been developed. The hardware and software architecture of this starter and its starting aspects are described. The programmable automation provided here allows a flexibility in algorithms which can be altered or expanded easily. The performance goals designed also include protection of induction motor against overload, phase loss, wrong phase sequence and severe over voltage due to self-excitation.  相似文献   
47.
In this paper we establish the log-convexity of the rate region in 802.11 WLANs. This generalises previous results for Aloha networks and has immediate implications for optimisation based approaches to the analysis and design of 802.11 wireless networks.  相似文献   
48.
Global query execution in a multidatabase system can be done parallelly, as all the local databases are independent. In this paper, a cost model that considers parallel execution of subqueries for a global query is developed. In order to obtain maximum parallelism in query execution, it is required to find a query execution plan that is represented in the form of a bushy tree and this query tree should be balanced to the maximal possible extent with respect to execution time. A new bottom up approach called Agglomerative Approach (AA) is proposed to construct balanced bushy trees with respect to execution time. By the deterministic nature of this approach, it generates local optimal solutions. This local minima problem will be severe in the case of graph queries, i.e., queries that are represented with a graph structure. A Simulated annealing Approach (SA) is employed to obtain a (near) optimal solution. These approaches (AA and SA) are suitable for handling on-line and off-line queries respectively. A Hybrid Approach (HA), that is an integration of AA and SA, is proposed to optimize queries for which the estimated time to be spent on optimization is known a priori. Results obtained with AA and SA on both tree and graph structured queries are presented.  相似文献   
49.
Autonomous vehicles equipped with integrity augmentation systems offer the potential to increase safety, efficiency and sustainability of airport ground operations. The model predictive behavior of these systems supports a timely detection of any deviations from the Required Navigation Performance (RNP), producing useful alerts for onboard mission management. Firstly, the system architecture of a Navigation and Guidance System (NGS) for autonomous airport surface vehicle operations based on Global Navigation Satellite System (GNSS) measurements is described. Subsequently, an integrity augmentation module is implemented in the NGS by modeling the key GNSS signal degradation phenomena including masking, multipath and signal attenuation. The GNSS integrity augmentation system is capable of monitoring the RNP and alerting the remote operator of the airport surface vehicle. The uniqueness of the presented system is that both caution and warning flags are produced based on prediction-avoidance and reaction-correction capabilities respectively. Additionally, the system is capable of issuing suitable steering commands to the onboard mission management system/remote ground base station operator in the event of GNSS signal degradations or losses. Multipath is modelled in detail using a ray tracing algorithm and the vehicle position error is computed as a function of relative geometry between the satellites, receiver antenna and reflectors in realistic airport operation scenarios. Additionally, the surface vehicle dynamics and reflective surfaces of buildings are modelled in order to simulate a vehicle trajectory through a typical airport airside/aprons environment. Simulation case studies are performed to validate the mathematical models developed for the integrity augmentation system and the results corroborate the suitability of the proposed system to generate useful and timely integrity flags when GNSS is used as the primary means of navigation.  相似文献   
50.
The Capacitated Arc Routing Problem (CARP) stands among the hardest combinatorial problems to solve or to find high quality solutions. This becomes even more true when dealing with large instances. This paper investigates methods to improve on lower and upper bounds of instances on graphs with over 200 vertices and 300 edges, dimensions that, today, can be considered of large scale. On the lower bound side, we propose to explore the speed of a dual ascent heuristic to generate capacity cuts. These cuts are next improved with a new exact separation enchained to the linear program resolution that follows the dual heuristic. On the upper bound, we implement a modified Iterated Local Search procedure to Capacitated Vehicle Routing Problem (CVRP) instances obtained by applying a transformation from the CARP original instances. Computational experiments were carried out on the set of large instances generated by Brandão and Eglese and also on the regular size sets. The experiments on the latter allow for evaluating the quality of the proposed solution approaches, while those on the former present improved lower and upper bounds for all instances of the corresponding set.  相似文献   
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