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991.
AIMS: Abdominal aortic aneurysms are characterised by changes in the extracellular matrix of the arterial media, in particular a reduction in elastin concentration. These changes are mediated by increased levels of endogenous matrix metalloproteinases (MMPs). Recently, calcium channel blockers have been shown to increase the proteolytic activity of MMP-2 secreted by vascular smooth muscle cells. It may therefore by hypothesised that calcium antagonists may potentiate the activity of MMPs in aneurysmal disease and thus accelerate AAA expansion. In this study, the ability of amlodipine--a calcium antagonist--to influence elastin degradation, was assessed in a previously described model of aneurysmal disease. METHODS: Porcine aortic segments (n = 8) were pre-incubated in exogenous pancreatic elastase for 24 h prior to culture in standard conditions for 6 days with 10 and 100 micrograms/l amlodipine. Control segments were cultured both with and without amlodipine and without elastase. At the termination of culture MMPs were extracted from the tissue and quantified by a combination of substrate gel enzymography and immunoblotting. The volume fractions of elastin and collagen were determined by stereological analysis of EVG stained sections. RESULTS: Gel enzymography demonstrated significantly increased MMP-9 activity in the amlodipine treated segments, median 4.218 vs. 2.809 arbitrary units (p < 0.01) and this elevated activity was reflected in a significant destruction of medial elastin 27.0 vs. 40.5% (p < 0.05). CONCLUSION: Therapeutic ranges of amlodipine significantly enhanced elastin degradation and potentiated MMP-9 activity within the aortic organ cultures.  相似文献   
992.
In chemical processing, it is important to distinguish between and identify polymorphic forms. We demonstrate the novel use of scanning thermal microscopy (SThM) and localized thermal analysis to distinguish and identify polymorphic forms of the drug cimetidine. These forms cannot be resolved by classical bulk thermal analysis. SThM reveals a sample consisting of a 50 : 50 mixture of the polymorphs contains regions of different thermal conductivity, corresponding to the different polymorphs. Localized thermal analysis of small volumes of pure polymorphic samples (approximately 50 µm3) shows that the origin of the thermal conductivity contrast lies, at least in part, with the presence of a surface water layer on the more hydrophilic polymorph.  相似文献   
993.
The results of a research program carried out to quantify the reliability of joint moldings for dc operation in submarine telecommunications cables are reported. The region of the bulk insulation most at risk of electrical failure has been identified as the amalgamation zone of the molding, which is believed to be associated with additional electrical stress-enhancing defects present at the conductor-insulator interface. In addition to factory tests implemented to eliminate moldings with severely hazardous defects, a quality assurance sampling test procedure is proposed to optimize the manufacturing quality  相似文献   
994.
On-line dynamic experiments on skeletal muscle vascular resistance require an extensive number of simple calculations in order to derive the data. A low-cost analog computer is described which utilizes perfusion pressure, venous flow, and muscle weight to calculate vascular resistance per 100 gm of muscle weight. This computer has been in use with the isolated perfused canine gracilis muscle preparation and has been shown to have considerable merit in reducing calculations and permitting immediate evaluation of the experimental data. A drop rate meter is incorporated in the device for the calculation of venous flow; perfusion pressure is obtained from a standard commercial transducer. A block diagram is included, and typical data are shown which illustrate the usefulness of continuous on-line calculation of resistance.  相似文献   
995.
996.
Isothermal titration calorimetry (ITC) measurements were performed on the binding of alpha methyl-D-mannopyranoside, D-mannopyranose, alpha methyl-D-glucopyranoside, and D-glucopyranose (Glu) to cobalt, nickel, and cadmium substituted concanavalin A (Con A) derivatives at pH = 6.9 and at 25 degrees C. The metal substituted Con A derivatives consisted of Co2+, Ni2+, and Cd2+ substituted for the Mn2+ ion in the S1 site of Con A which is about 12.8 A away from the center of the carbohydrate binding site of Con A. The thermodynamic quantities determined from the ITC measurements were the same for most of the binding reactions indicating that the structure of the binding site in solution is the same for all the Con A derivatives in solution and that the presence of different 2+ metal ions in the S1 site has little effect on the binding reactions. Differential scanning calorimetry scans of solutions of the metal ion derivatives of Con A show that the thermodynamics of the unfolding transition for the cobalt and nickel substituted derivatives are the same as for Con A: they dissociate from tetramers into monomers as they unfold around 85 degrees C. The cadmium substituted Con A derivative, however, exhibits an additional transition around 93 degrees C which also appears following the addition of Cd2+ to the Con A solutions. This transition results from the unfolding of a species of Con A with Cd2+ substituted into a third binding site at the monomeric interface of the Con A tetramer. The higher stability of this species is not only exemplified by the higher thermal transition temperature but also by the lack of dissociation as it unfolds. Cd2+ is released from the S3 site upon decreasing the pH from 6.9 to 6.4. ITC measurements on the binding reaction of Cd2+ to Con A show that the binding enthalpy is 40.2 +/- 0.4 kJ mol-1 at 23.4 +/- 0.2 degrees C and the binding reaction exhibits a large heat capacity change of 1.43 +/- 0.41 kJ mol-1 K-1.  相似文献   
997.
998.
BACKGROUND: Although the public perceives video-assisted thoracic surgery (VATS) as advantageous because it is less invasive than a thoracotomy, the medical community has questioned the safety of VATS lobectomy and its adequacy as a cancer operation. Reported series have not been able to address these issues because follow-up has been only short-term. METHODS: A multiinstitutional, retrospective review was performed in 298 consecutive patients who underwent VATS for a standard anatomic lobectomy with lymph node dissection for lung cancer. Pathologic staging was I in 233 (78%), II in 27 (9%), and IIIA in 38 (13%) patients. Kaplan Meier survival analysis was performed. RESULTS: The conversion rate from VATS lobectomy to thoracotomy was 6%, but none were for massive intraoperative bleeding. The only death (0.3%) was because of mesenteric venous thrombosis. Forty minor complications occurred in 38 patients (12.8%) undergoing VATS. The mean and median lengths of stay were 5+/-3.39 and 4 days, respectively. Recurrence in an incision occurred in 1 patient (0.3%). The Kaplan Meier 4-year survival for stage I was 70%+/-5%. CONCLUSION: The VATS lobectomy for bronchogenic carcinoma appears to be a safe operation, with the same survival as expected for a lobectomy done by thoracotomy.  相似文献   
999.
The synucleins are a unique family of small intracellular proteins that have recently attracted considerable attention because of their involvement in human neurodegenerative diseases. We have cloned a new member of the synuclein family called persyn. In contrast to other synucleins, which are presynaptic proteins of CNS neurons, persyn is a cytosolic protein that is expressed predominantly in the cell bodies and axons of primary sensory neurons, sympathetic neurons, and motoneurons. Northern blotting, in situ hybridization, Western blotting, and immunohistochemistry revealed that persyn mRNA and protein are expressed in these neurons from the earliest stages of axonal outgrowth and are maintained at a high level throughout life. Persyn also becomes detectable in evolutionary recent regions of the brain by adulthood.  相似文献   
1000.
We propose a resource-efficient way to execute requests in Byzantine-fault-tolerant replication that is particularly well-suited for services in which request processing is resource-intensive. Previous efforts took a failure masking all-active approach of using all execution replicas to execute all requests; at least 2t + 1 execution replicas are needed to mask t Byzantine-faulty ones. We describe an asynchronous protocol that provides resource-efficient execution by combining failure masking with imperfect failure detection and checkpointing. Our protocol is parsimonious since it uses only t + 1 execution replicas, called the primary committee or PC, to execute the requests under normal conditions characterized by a stable network and no misbehavior by PC replicas; thus, a trustworthy reply can be obtained with the same latency, but with only about half of the overall resource use of the all-active approach. However, a request that exposes faults among the PC replicas causes the protocol to switch to a recovery mode, in which all 2t + 1 replicas execute the request and send their replies; then, after selecting a new PC, the protocol switches back to parsimonious execution. Such a request incurs a higher latency using our approach than the all-active approach, mainly because of fault detection latency. Practical observations point to the fact that failures and instability are the exception rather than the norm. That motivated our decision to optimize resource efficiency for the common case, even if it means paying a slightly higher performance cost during periods of instability  相似文献   
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