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101.
Extensive restriction site polymorphism at the human phenylalanine hydroxylase locus and application in prenatal diagnosis of phenylketonuria 总被引:4,自引:0,他引:4
AS Lidsky FD Ledley AG DiLella SC Kwok SP Daiger KJ Robson SL Woo 《Canadian Metallurgical Quarterly》1985,37(4):619-634
A total of 10 restriction site polymorphisms have been identified at the human phenylalanine hydroxylase locus using a full-length human phenylalanine hydroxylase cDNA clone as a hybridization probe to analyze human genomic DNA. These polymorphic patterns segregate in a Mendelian fashion and concordantly with the disease state in various PKU kindreds. The frequencies of the restriction site polymorphisms at the human phenylalanine hydroxylase locus among Caucasians are such that the observed heterozygosity in the population is 87.5%. Thus, most families with a history of classical phenylketonuria can take advantage of the genetic analysis for prenatal diagnosis and carrier detection of the hereditary disorder. 相似文献
102.
JD Reveille GS Alarcón SE Fowler SR Pillemer R Neuner DO Clegg IS Mikhail DE Trentham JC Leisen G Bluhm SM Cooper H Duncan M Tuttleman SP Heyse JT Sharp B Tilley 《Canadian Metallurgical Quarterly》1996,39(11):1802-1807
OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA. 相似文献
103.
The role of vasoactive intestinal peptide (VIP) was investigated when mucosal stroking and 5-hydroxytryptamine (5-HT) were used to activate neural reflexes that stimulate chloride secretion in the guinea pig colon. Muscle-stripped segments of colon containing intact submucosal ganglia without myenteric ganglia were set up in modified flux chambers in order to record short-circuit current (Isc). Mucosal stroking with a brush for 1 s or a pulse of 5-HT (injection of 15 microliters of 100 microM 5-HT into 1.5 ml of mucosal solution) caused an increase in Isc that was reduced by the VIP antagonist, neurotensin6-11-VIP7-28, in a concentration-dependent manner. The Isc responses to mucosal stroking and a 5-HT pulse were reduced by 53% and 58%, respectively, by 2 microM neurotensin6-11-VIP7-28. The residual Isc response in the presence of neurotensin6-11-VIP7-28 was abolished by atropine. Blockade of 5-HT1P receptors on submucosal afferent neurons decreased Isc responses to stroking or a 5-HT pulse. The residual Isc response after 5-HT1P receptors were blocked was reduced by only 11-14% by neurotensin6-11-VIP7-28. In the presence of blockade of both 5-HT1P and VIP receptors, atropine abolished the Isc response to both stimuli. The observations suggest that the neural circuitry activated by stroking includes at least two independent pathways. One pathway contains VIP neurons which receive inputs directly or indirectly from 5-HT1P receptor-containing afferents. A second pathway involves muscarinic cholinergic transmission that is independent of 5-HT1P and VIP receptor activation. 相似文献
104.
P. PAPANIKOS K. I. TSERPES SP. PANTELAKIS 《Fatigue & Fracture of Engineering Materials & Structures》2003,26(1):37-47
A progressive fatigue damage model has been developed for predicting damage accumulation and life of carbon fibre‐reinforced plastics (CFRP) laminates with arbitrary geometry and stacking sequence subjected to constant amplitude cyclic loading. The model comprises the components of stress analysis, fatigue failure analysis and fatigue material property degradation. Stress analysis of the composite laminate was performed by creating a three‐dimensional finite element model in the ANSYS FE code. Fatigue failure analysis was performed by using a set of Hashin‐type failure criteria and the Ye‐delamination criterion. Two types of material property degradations on the basis of element stiffness and strength were applied: a sudden degradation because of sudden failure detected by the fatigue failure criteria and a gradual degradation because of the nature of cyclic loading, which is driven by the increased number of cycles. The gradual degradation of the composite material was modelled by using functions relating the residual stiffness and residual strength of the laminate to the number of cycles. All model components have been programmed in the ANSYS FE code in order to create a user‐friendly macro‐routine. The model has been applied in two different quasi‐isotropic CFRP laminates subjected to tension–compression (T–C) fatigue and the predictions of fatigue life and damage accumulation as a function of the number of cycles were compared with experimental data available in the literature. A very good agreement was obtained. 相似文献
105.
Distinct stability of recombinant L and H subunits of human ferritin: calorimetric and ANS binding studies 总被引:1,自引:0,他引:1
Thermodynamic and pH stability of recombinant human L- and H-ferritins wereprobed by differential scanning calorimetry and 8-anilino-1-naphthalenesulfonate (ANS) binding in the pH range 2-7. At pH 2.0-2.8 theywere dissociated into subunit monomers and in this pH interval theH-subunit displayed a single calorimetrically-revealed domain withproperties of a molten globule-like state: low enthalpy (6.3-8.0 J/g or169-172 kJ/mol) and Tm of thermal unfolding (approximately 50 degrees C), awide transition range (approximately 20 degrees C) and high ANS binding. Incontrast, at pH 2 the L-ferritin subunit showed two calorimetric domainswith Tm of 35 and 40 degrees C with similar unfolding enthalpies and withmoderate extent of interactions, as indicated by the ratio of calorimetricenthalpy (293.9 kJ/mol) and van't Hoff enthalpy (174.2 kJ/mol) for thethermal transition. A pH increase from 2.0 to 2.8 determined the couplingof the two domains into a single cooperative folding unit and drasticincrease of the transition temperature (from 37 to 80 degrees C). Thecontacts between the two domains in the L-subunit appeared to contribute toabout 30% of the total stabilization free energy. The unfolding enthalpies,heat capacity changes and pronounced ANS binding of the L-subunit at pH2.0- 2.8 indicated that part of the structure lacked 'meltable' tertiaryinteractions. The results indicate that H- and L-subunits are stabilized bylargely different intra-chain interactions with a critical contribution toL-subunit stability of embedded salt bridge(s) absent in the H-subunit. 相似文献
106.
By homology to the mgt gene (encoding a macrolide glycosyltransferase) from Streptomyces lividans, a 3.3-kb DNA fragment from the oleandomycin producer, Streptomyces antibioticus, was cloned and sequenced. Analysis of the sequence revealed the presence of the 3' end of a gene (ORF1) and two complete ORFs (ORF2 and oleD), all of them translationally coupled. The deduced product of the sequenced region of ORF1 contained the typical signature of integral membrane proteins responsible for the translocation of substrates across the membrane. The ORF2 product did not show significant similarity with proteins in databases, but contains an N-terminus leader peptide region characteristic of secreted proteins, and a lipid attachment site motif characteristic of membrane lipoproteins synthesized with a precursor signal peptide. The oleD product showed clear similarity with several UDP-glucuronosyl- and UDP-glycosyl-transferases from different origins and particularly with the mgt gene from S. lividans, and might encode a glycosyltransferase activity capable of inactivating macrolides. It is proposed that these three genes could participate in the intracellular glycosylation of oleandomycin and its secretion during antibiotic production. 相似文献
107.
DB Sarwer SP Bartlett LA Whitaker KT Paige MJ Pertschuk TA Wadden 《Canadian Metallurgical Quarterly》1999,103(2):412-418
This study represents an initial investigation into the adult psychological functioning of individuals born with craniofacial disfigurement. A total of 24 men and women born with a craniofacial anomaly completed paper and pencil measures of body image dissatisfaction, self-esteem, quality of life, and experiences of discrimination. An age- and gender-matched control group of 24 non-facially disfigured adults also completed the measures. As expected, craniofacially disfigured adults reported greater dissatisfaction with their facial appearance than did the control group. Craniofacially disfigured adults also reported significantly lower levels of self-esteem and quality of life. Dissatisfaction with facial appearance, self-esteem, and quality of life were related to self-ratings of physical attractiveness. More than one-third of craniofacially disfigured adults (38 percent) reported experiences of discrimination in employment or social settings. Among disfigured adults, psychological functioning was not related to number of surgeries, although the degree of residual facial deformity was related to increased dissatisfaction with facial appearance and greater experiences of discrimination. Results suggest that adults who were born with craniofacial disfigurement, as compared with non-facially disfigured adults, experience greater dissatisfaction with facial appearance and lower self-esteem and quality of life; however, these experiences do not seem to be universal. 相似文献
108.
E Vittinghoff S Scheer P O'Malley G Colfax SD Holmberg SP Buchbinder 《Canadian Metallurgical Quarterly》1999,179(3):717-720
The reasons for recent declines in AIDS incidence and mortality may include advances in treatment, but these may be confounded by earlier declines in the incidence of human immunodeficiency virus (HIV) infection. To determine whether the declines in AIDS and mortality may, in part, stem from wider use of combination antiretroviral therapy, 622 HIV-positive men with well-characterized dates of seroconversion were followed. In this group, combination therapy came into widespread use in only 1996. In a Cox proportional hazards model, the 1996 calendar period was significantly associated with slower progression to AIDS (relative hazard [RH]=0. 19, 95% confidence interval [CI], 0.05-0.69, P=.01) and death (RH=0. 45, 95% CI, 0.21-0.95, P=.04). Declines in incidence of HIV infection, changes in HIV virulence, and end-point underreporting cannot fully explain the decline in AIDS and death in 1996. The introduction of combination antiretroviral therapy as the standard of care may already have had measurable effects. 相似文献
109.
SP Hams 《Canadian Metallurgical Quarterly》1997,13(6):351-356
The presence in serum of adenylate kinase isoenzyme originating from erythrocyte can be useful as a marker for detecting hemolysis. We have presented preliminary evidence for identifying hemolytic anemia patients earlier by determining erythrocyte AK isoenzyme activity in serum (or plasma) rather than using measurement of plasma hemoglobin concentration. This test being quite specific for hemolysis should find use as a quick method for estimating the extent of in vivo hemolysis in hemolytic patients earlier than heretofore possible. 相似文献
110.