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1.
Magnetic resonance imaging of the pediatric airway 总被引:1,自引:0,他引:1
FL Rimell AM Shapiro MP Meza S Goldman S Hite B Newman 《Canadian Metallurgical Quarterly》1997,123(9):999-1003
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MG Newman 《Canadian Metallurgical Quarterly》1997,2(1):180-198
The design and implementation of clinical trials (CTs) carried out to evaluate antimicrobial and anti-infective drugs and devices are one of the most difficult challenges in contemporary periodontal research and product development. The overwhelming amount of evidence which has established a microbial etiology for periodontitis is the basis for developing and testing antimicrobial treatments. Well-designed antimicrobial CTs start with a carefully crafted hypothesis and a protocol which explicitly integrates the requirements of the patient, the clinician, the sponsor, and regulatory authorities. Surrogate variables for effectiveness must be clinically relevant, scientifically sound, and statistically valid. Currently, clinical attachment level measurements and alveolar bone assessments are accepted as proof of effectiveness. Indication and claim support of the antimicrobial product guide the design and implementation of the CT. Adverse microbiologic consequences, such as lack of antimicrobial susceptibility, wrong spectrum, incorrect dosage, non-compliance, and drug interference, must be monitored. Successful CTs balance a large group of variables used to screen, randomize, and assign subjects to experimental and control groups to ensure that prognostic and risk factors are properly accounted for. 相似文献
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SM Kornblau E Estey T Madden HT Tran S Zhao U Consoli V Snell G Sanchez-Williams H Kantarjian M Keating RA Newman M Andreeff 《Canadian Metallurgical Quarterly》1997,15(5):1796-1802
PURPOSE: Expression of the multidrug resistance gene (MDR1) p170 protein is frequent in leukemic blasts from patients with relapsed acute myelogenous leukemia (AML). A phase I study using the nonimmunosuppressive MDR1 blocker SDZ PSC-833 (PSC) in combination with mitoxantrone (MITO) and etoposide (VP) was performed. PATIENTS AND METHODS: Starting doses (LVL0) of MITO (3.25 mg/m2/d on days 1 and 3 to 6) and VP (210 mg/m2/d on days 1 and 3 to 5) were 40% of the maximal-tolerated dose (MTD) from a prior study. A 1.5-mg/kg loading dose of PSC was followed by a 120-hour continuous infusion of 10 mg/kg/d on days 2 to 6. Blood samples for PSC, MITO, and VP pharmacokinetics (PK) were taken on days 1 and 3, and samples for MDR1 expression were taken on day 0. RESULTS: Severe mucositis developed in all patients at LVL0; therefore, MITO and VP doses were reduced to 2.5 and 170 mg/m2 (LVL-1) for the next seven patients, and this dose proved to be MTD. All LVL0 and three LVL-1 patients had transient elevations in the serum bilirubin level to > or = 4 mg/dL. Serum creatinine level increased to greater than 2 mg/dL in one case. There were no other grade 3 or 4 nonhematologic toxicities observed. The peripheral blood was cleared of leukemia in three LVL0 and four LVL-1 patients. The marrow was cleared of leukemic cells in one LVL0 and five LVL-1 patients, and a significant reduction in marrow leukemic infiltrate was observed in eight of 10. No patient achieved complete remission (CR), and all died of progressive disease (n = 8) or infection (n = 2). MDR1 expression was detected by fluorescent-activated cell sorter (FACS) analysis in five of seven cases. An elevated MDR1 mRNA level was detected by quantitative polymerase chain reaction (Q-PCR) in six of eight cases studied. Clearing of leukemia cells from the marrow occurred in four of six MDR1-positive and one of three MDR1-negative patients. Despite the fact that LVL0 doses had to be reduced due to toxicity, coadministration of PSC did not produce a consistent effect on MITO PK; however, it did repeatedly lead to increased levels of VP in the serum. CONCLUSION: We conclude that PSC-MITO-VP is a tolerable regimen with antileukemic activity. Addition of PSC necessitated a 66% reduction in MITO and VP doses from a prior study without PSC. 相似文献
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RA Newman JC Vidal LJ Viskatis J Johnson MA Etcheverry 《Canadian Metallurgical Quarterly》1993,11(2-3):151-159
Two purified animal venom toxins, crotoxin and cardiotoxin, have been combined to produce a unique natural product (VRCTC-310) currently under investigation as an antitumor agent by the National Cancer Institute. In vitro, it has demonstrated cytotoxic disease specificity and a unique mechanism of action when submitted to COMPARE analysis. In vivo, tolerance was developed to the neurotoxic properties of crotoxin which allowed comparison of several schedules of fixed and escalating daily i.m. doses to mice bearing s.c. Lewis Lung carcinoma. An 83% inhibition of tumor growth was achieved using an escalating dose schedule starting at 1.8 mg/kg and reaching 6.3 mg/kg/day on day 20. Although some irritation around the sites of i.m. injection was noted, animal weight loss was negligible and there were no other signs of adverse toxicity. This natural product represents a new, membrane interactive anticancer agent which produces a unique spectrum of cytotoxicity in vitro and which has demonstrated interesting in vivo antitumor efficacy. 相似文献
8.
An adaptive product platform offers high customizability for generating feasible product variants for customer requirements. Customization takes place not only to product platform structure but also to its relevant parameters. Structural and parametric optimization processes are interwoven with each other to achieve the total optimality. This paper presents an evolutionary method dealing with interwoven structural and parametric optimization of adaptive platform product customization. The method combines genetic programming and genetic algorithm for handling structural and parametric optimization, respectively. Efficient genetic representation and operation schemes are carefully adapted. While designing these schemes, features specific to structural and parameter customization are considered for the simplification of platform product management. The experimental results show that the performance of the proposed algorithm outperforms that of the tandem evolutionary algorithm in which a genetic algorithm for parametric optimization is totally nested in a genetic programming for structural optimization. 相似文献
9.
M. L. Newman B. J. Robinson H. Sehitoglu J. A. Dantzig 《Metallurgical and Materials Transactions A》2003,34(7):1483-1491
A study of the development of deformation and transient and residual stresses during quenching in aluminum alloy W319 is presented.
Rapid tension tests were performed on W319 in the super-saturated solution state at several temperatures and strain rates.
A material model following the mechanical threshold stress (MTS)-Voce formulation is developed and implemented in both a simple
one-dimensional code and a fully three-dimensional form as a user material subroutine in ABAQUS. The results of the tension
tests are used to determine the parameters in the thermomechanical constitutive model. Unidirectional beam quenching experiments
are performed to test the applicability of the constitutive model. Residual stresses in the beams are measured using a groove
removal technique upon completion of the quenching process. Residual stress and deformation results from beam quenching experiments
compare well to the analytical results computed using the constitutive model. 相似文献
10.
T Peelen M van Vliet A Petrij-Bosch R Mieremet C Szabo AM van den Ouweland F Hogervorst R Brohet MJ Ligtenberg E Teugels R van der Luijt AH van der Hout JJ Gille G Pals I Jedema R Olmer I van Leeuwen B Newman M Plandsoen M van der Est G Brink S Hageman PJ Arts MM Bakker P Devilee 《Canadian Metallurgical Quarterly》1997,60(5):1041-1049
We have identified 79 mutations in BRCA1 in a set of 643 Dutch and 23 Belgian hereditary breast and ovarian cancer families collected either for research or for clinical diagnostic purposes. Twenty-eight distinct mutations have been observed, 18 of them not previously reported and 12 of them occurring more than once. Most conspicuously, a 2804delAA mutation has been found 19 times and has never been reported outside the Netherlands. A common haplotype spanning > or = 375 kb could be identified for each of the nine examined recurrent mutations, indicating the presence of multiple BRCA1 founder mutations in the Dutch population. The 2804delAA mutation has been estimated to have originated approximately 32 generations ago. No specific breast or ovarian cancer phenotype could be assigned to any of the common mutations, and the ovarian cancer incidence among 18 families with the 2804delAA mutation was heterogeneous. 相似文献