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DP McHale S Mitchell S Bundey L Moynihan DA Campbell CG Woods NJ Lench RF Mueller AF Markham 《Canadian Metallurgical Quarterly》1999,64(2):526-532
Cerebral palsy has an incidence of approximately 1/500 births, although this varies between different ethnic groups. Genetic forms of the disease account for approximately 1%-2% of cases in most countries but contribute a larger proportion in populations with extensive inbreeding. We have clinically characterized consanguineous families with multiple children affected by symmetrical spastic cerebral palsy, to locate recessive genes responsible for this condition. The eight families studied were identified from databases of patients in different regions of the United Kingdom. After ascertainment and clinical assessment, we performed a genomewide search for linkage, using 290 polymorphic DNA markers. In three families, a region of homozygosity at chromosome 2q24-q25 was identified between the markers D2S124 and D2S148. The largest family gave a maximum LOD score of 3.0, by multipoint analysis (HOMOZ). The maximum combined multipoint LOD score for the three families was 5.75. The minimum region of homozygosity is approximately 5 cM between the markers D2S124 and D2S2284. We have shown that a proportion of autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. The identification of genes involved in the etiology of cerebral palsy may lead to improved management of this clinically intractable condition. 相似文献
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L Liberman N Bracero MA Vuolo DD Dershaw EA Morris AF Abramson PP Rosen 《Canadian Metallurgical Quarterly》1999,172(2):331-337
Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae possess the ability to cleave human IgA1 antibodies, and all successfully colonize and occasionally invade the human upper respiratory tract. N. meningitidis invades the bloodstream after a period of nasopharyngeal colonization. We directly compared levels of IgA1 protease activity in strains (n=52) derived from the cerebrospinal fluid or blood of patients with meningococcal disease with strains of N. meningitidis obtained from asymptomatic carriers (n=25). IgA1 protease activity was determined by a sensitive semiquantitative ELISA assay. Levels of IgA1 protease activity were significantly higher (P<0.0001) in strains associated with invasive meningococcal disease (98% with detectable activity, mean = 580 mU) than with those obtained from asymptomatic carriers (76% with detectable activity, mean = 280 mU). Despite marked variation in enzyme activity, almost all strains (96%) possessed the gene for IgA1 protease. Given the panmictic population structure of the bacterial isolates investigated, these data, obtained from two groups infected with N. meningitidis, but with markedly different clinical outcomes, provide the first quantitative evidence that IgA1 protease activity is a virulence determinant that contributes to the pathogenic phenotype, and suggest IgA1 protease as a potential target for prophylaxis. 相似文献
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Expression of c-fos mRNA was studied in the adult rat brain following cochlear ablations by using in situ hybridization. In normal animals, expression was produced by acoustic stimulation and was found to be tonotopically distributed in many auditory nuclei. Following unilateral cochlear ablation, acoustically driven expression was eliminated or decreased in areas normally activated by the ablated ear, e.g., the ipsilateral dorsal and ventral cochlear nuclei, dorsal periolivary nuclei, and lateral nucleus of the trapezoid body and the contralateral medial and ventral nuclei of the trapezoid body, lateral lemniscal nuclei, and inferior colliculus. These deficits did not recover, even after long survivals up to 6 months. Results also indicated that neurons in the dorsal cochlear nucleus could be activated by contralateral stimulation in the absence of ipsilateral cochlear input and that the influence of the contralateral ear was tonotopically organized. Results also indicated that c-fos expression rose rapidly and persisted for up to 6 months in neurons in the rostral part of the contralateral medial nucleus of the trapezoid body following a cochlear ablation, even in the absence of acoustic stimulation. This response may reflect a release of constitutive excitatory inputs normally suppressed by missing afferent input or changes in homeostatic gene expression related to sensory deprivation. Instances of transient, surgery-dependent increases in c-fos mRNA expression in the absence of acoustic stimulation were observed in the superficial dorsal cochlear nucleus and the cochlear nerve root on the ablated side. 相似文献
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STUDY DESIGN: The canal space of burst-fractured, human cervical spine specimens was monitored to determine the extent to which spinal position affected post-injury occlusion. OBJECTIVE: To test the null hypothesis that there is no difference in spinal canal occlusion as a function of spinal positioning for a burst-fractured cervical spine model. SUMMARY OF BACKGROUND DATA: Although previous studies have documented the effect of spinal positioning on canal geometry in intact cadaver spines, to the authors' knowledge, none has examined this relationship specifically in a burst fracture model. METHODS: Eight human cervical spine specimens (levels C1 to T3) were fractured by axial impact, and the resulting burst injuries were documented using post-injury radiographs and computed tomography scans. Canal occlusion was measured using a custom transducer in which water was circulated through a section of flexible tygon tubing that was passed through the spinal canal. Any impingement on the tubing produced a rise in fluid pressure that was monitored with a pressure transducer. Each spine was positioned in flexion, extension, lateral (and off-axis) bending, axial rotation, traction, and compression, while canal occlusion and angular position were monitored. Occlusion values for each position were compared with measurements taken with the spine in neutral position. RESULTS: Compared with neutral position, compression, extension, and extension combined with lateral bending significantly increased canal occlusion, whereas flexion decreased the extent of occlusion. In extension, the observed mechanism of occlusion was ligamentum flavum bulge caused by ligament laxity resulting from reduced vertebral body height. CONCLUSIONS: Increased compression of the spinal cord after injury may lead to more extensive neurologic loss. This study demonstrated that placing a burst-fractured cervical spine into either extension or compression significantly increased canal occlusion as compared with occlusion in a neutral position. 相似文献
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The steady-state kinetics of the ThTP hydrolysis by thiamine triphosphatase (EC 3.6.1.28) from bovine brain testified to the presence of two kinetically significant conformational states of the protein, their equilibrium being determined by the substrate concentration. The ThTPase isomeric forms had different activities, affinities for ThTP and activation energies. The form with high affinity for the substrate was characterized by the Km and Vmax values of 43 microM and 9.9 mumol.s-1.mg-1 whereas for the form with lower affinity these values were equal to 298 microM and 19.3 mumol.s-1.mg-1, respectively. The activation energies of the ThTP hydrolysis reactions were 85.3 and 47.1 kJ.mol-1. Several mechanisms of the enzyme activity regulation in the cell are suggested. One of the mechanisms is related to the allosteric ThTP effect inducing reversible transition of the protein to a more active conformational state, while the others include the inhibition activity by ATP and the activation of ThTP-ase by Mg2+ free ions. 相似文献