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81.
Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours.  相似文献   
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83.
Hormone-refractory prostate cancer (HRPC) patients often have nonmeasurable disease. In such patients, predictive biomarkers other than tumor response may be required to compare therapeutic effects. We examined the predictive value for survival of various clinical and laboratory parameters, including prostate-specific antigen (PSA), in HRPC patients treated with suramin. Data from 103 HRPC patients were analyzed using various survival analyses, the likelihood ratio approach, and logistic regression analyses. When pretreatment factors, percentage decrease in PSA at 4 weeks from start of treatment (deltaPSA), and updated survival data were fit by a multivariate Cox proportional hazards model, acid phosphatase, lactate dehydrogenase, and deltaPSA were significant, with risk ratios close to 1. There was a decrease in likelihood ratio with increasing APSA. A logistic regression model was developed to predict the probability of <1 year of survival from the start of treatment. Hemoglobin and deltaPSA were found to be significant variables. However, in view of the complexities involving the relationship between PSA expression and prostate cancer growth and possible selective effect of treatment on PSA, further prospective testing is necessary. Therefore, deltaPSA cannot necessarily be used as a biomarker for survival response in individual patients during the evaluation of the therapeutic response of HRPC to new antineoplastic drugs.  相似文献   
84.
The purpose of this study was to investigate platelet effects on postischemic heart function in conjunction with adenosine effects on intracoronary platelet adhesion. Homologous platelets were infused into the coronaries of isolated guinea pig hearts, either during low-flow ischemia or during reperfusion, and external heart work (EHW) and intracoronary platelet adhesion were determined. In most experiments, thrombin was added to the perfusate. The influence of endogenous adenosine was studied by use of the uptake blocker dipyridamole and the unspecific adenosine-receptor blocker theophylline, the A1-receptor blocker 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), and the A2-receptor blocker 3,7-dimethyl-1-propargylxanthine (DMPX). The importance of nitric oxide and prostaglandin I2 (PGI2) was tested by using nitro-L-arginine (NOLAG) and indomethacin, respectively. When platelets were applied with thrombin during low-flow ischemia, EHW recovered to only 63 +/- 4% of the preischemic value, as compared with 89 +/- 3% without platelets (p < 0.05). Despite thrombin, platelets incurred no significant functional loss when applied in the first minute of reperfusion (but again in the fifth minute); however, when theophylline was also present, recovery of EHW amounted to only 42 +/- 12%. Intracoronary adhesion of platelets was negligible without thrombin, and highest during low-flow ischemia with thrombin (35 +/- 3% of the applied number). No adhesion occurred during the first minute of reperfusion, whereas in the fifth minute, adhesion was again 20.8 +/- 4%. Dipyridamole increased adenosine release and attenuated adhesion at this time. Theophylline increased adhesion in the first minute of reperfusion (33 +/- 6.4%), whereas NOLAG and indomethacin proved to be ineffective. DPCPX and DMPX each increased platelet retention during the first minute of reperfusion, their effects being additive. Intracoronary adhesion of platelets induced by thrombin in isolated hearts can reduce postischemic recovery of heart function. During reperfusion, but not during low-flow, endogenous adenosine can prevent platelet adhesion and loss of myocardial function, an action mediated both by A1- and A2-receptor-dependent mechanisms.  相似文献   
85.
86.
This study was designed to examine whether cyclosporine (CyA) acts on the endocrine system by modifying the pulsatile secretion pattern of prolactin and LH. Both pituitary-grafted and sham-operated rats were submitted to a subcutaneous vehicle or CyA (5 mg/kg) treatment daily for 10 days beginning on the day of surgery. Pituitary grafting and/or CyA administration changed the pulsatile pattern of prolactin observed in sham-operated animals. The mean values of serum prolactin were significantly increased by pituitary grafting and the treatment with CyA further increased them. The mean half-life of prolactin was significantly increased in pituitary-grafted rats and was not changed by CyA administration, although it was decreased in sham-operated rats. The frequency of prolactin pulses was significantly decreased in pituitary-grafted as compared to sham-operated controls and was not further modified by CyA administration. However, in sham-operated rats a significant decrease of this parameter was observed. Duration of the prolactin peaks was significantly increased by pituitary grafting, and was not modified by CyA administration in any of the groups studied. The absolute amplitude of the prolactin peaks was significantly increased in pituitary-grafted as compared to sham-operated animals, and the treatment with CyA further increased this parameter in both groups. Mean values of LH were significantly increased in pituitary-grafted as compared to control rats. CyA administration significantly increased LH levels in sham-operated rats and decreased them in pituitary-grafted animals. The mean half-life, the pulse frequency and the duration of LH peaks were not modified by either pituitary grafting or CyA administration.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   
87.

Studying the changes of shape is a common concern in many scientific fields. We address here two problems: (1) quantifying the deformation between two given shapes and (2) transporting this deformation to morph a third shape. These operations can be done with or without point correspondence, depending on the availability of a surface matching algorithm, and on the type of mathematical procedure adopted. In computer vision, the re-targeting of emotions mapped on faces is a common application. We contrast here four different methods used for transporting the deformation toward a target once it was estimated upon the matching of two shapes. These methods come from very different fields such as computational anatomy, computer vision and biology. We used the large diffeomorphic deformation metric mapping and thin plate spline, in order to estimate deformations in a deformational trajectory of a human face experiencing different emotions. Then we use naive transport (NT), linear shift (LS), direct transport (DT) and fanning scheme (FS) to transport the estimated deformations toward four alien faces constituted by 240 homologous points and identifying a triangulation structure of 416 triangles. We used both local and global criteria for evaluating the performance of the 4 methods, e.g., the maintenance of the original deformation. We found DT, LS and FS very effective in recovering the original deformation while NT fails under several aspects in transporting the shape change. As the best method may differ depending on the application, we recommend carefully testing different methods in order to choose the best one for any specific application.

  相似文献   
88.

Contracts play an important role in business management where relationships among different parties are dictated by legal rules. Electronic contracts have emerged mostly due to technological advances and electronic trading between companies and customers. New challenges have then arisen to guarantee reliability among the stakeholders in electronic negotiations. In this scenario, automatic verification of electronic contracts appeared as an imperative support, specially the conflict detection task of multi-party contracts. The problem of checking contracts has been largely addressed in the literature, but there are few, if any, methods and practical tools that can deal with multi-party contracts using a contract language with deontic and dynamic aspects as well as relativizations, over the same formalism. In this work we present an automatic checker for finding conflicts on multi-party contracts modeled by an extended contract language with deontic operators and relativizations. Moreover a well-known case study of sales contract is modeled and automatically verified by our tool. Further, we performed practical experiments in order to evaluate the efficiency of our method and the practical tool.

  相似文献   
89.
Neural Computing and Applications - Grapes reception is a key process in wine production. The harvest days are extremely challenging days in managing the reception of the grapes, as the winery...  相似文献   
90.
In this paper, we verify how far electric disturbance signals can be compressed without compromising the analysis of encoded fault records. A recently proposed compression algorithm, referred to as Damped Sinusoidal Matching Pursuit (DSMP) has the remarkable feature of obtaining both compact and physically interpretable representations. However, for fault analysis applications, one is primarily interested in how accurate can be the analysis performed on compressed signals, instead of evaluating mean-squared error figures. Unlike previous works in digital fault records compression, the performance of the DSMP compression method is evaluated using a protocol based on fault analysis procedures commonly performed by expert engineers. This protocol is applied for comparing the results obtained in the analysis of both uncompressed records and their compressed versions at different compression ratios. The results show that the DSMP is a reliable compression system since it achieves high compression ratios (6.4:1) without causing fault analysis misinterpretation.  相似文献   
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