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排序方式: 共有641条查询结果,搜索用时 31 毫秒
621.
D Patel BD McKinley TP Davis F Porreca HI Yamamura VJ Hruby 《Canadian Metallurgical Quarterly》1997,8(3):434-441
As an approach to the development of therapeutically useful peptide pharmaceuticals that can penetrate the blood-brain barrier, we have designed and demonstrated the application of a carrier-targeting system. We have developed a prodrug design strategy that is designed to utilize membrane-bound enzymes whereby release of a bioactive peptide from a highly lipophilic triglyceride peptide-carrier is achieved in situ, thus attaining high localized concentrations of the bioactive peptide. Following localization of such a system, normal peptidase and lipase action is utilized to release the active peptide (deltorphin II) intact and in high concentration. At present, the exact mechanisms are unclear, but the observed results in which analgesia is observed following peripheral administration suggest that the active peptide is able to cross the blood-brain barrier and sustain prolonged periods of analgesia as determined by antinociception tests by release of the bioactive peptide. In vitro tests of binding and bioactivity by the peptide conjugate show essentially no potency in either target or control analogues, but potent antinociceptive effects are observed following peripheral administration. 相似文献
622.
HM Ruottinen JO Rinne VJ Oikonen JR Bergman MT Haaparanta OH Solin UH Ruotsalainen UK Rinne 《Canadian Metallurgical Quarterly》1997,27(4):336-346
The aim was to investigate the effects of inhibition of monoamine oxidase type B (MAO-B) with selegiline alone and the combined inhibition of peripheral catechol-O-methyltransferase (COMT) with entacapone and MAO-B with selegiline on striatal 6-[18F]fluorodopa (FDOPA) accumulation, and whether the effect of entacapone + selegiline on FDOPA uptake differed depending on the severity of the presynaptic dopaminergic dysfunction. Thus, eight healthy controls, eight de novo patients with Parkinson's disease (PD), and 18 levodopa-treated PD patients were investigated with positron emission tomography (PET). Half of the subjects in each population belonged to the selegiline group and half to the entacapone + selegiline group. Both groups were studied twice with PET using FDOPA. After the first (baseline) FDOPA PET investigation, both groups were on 2 weeks of selegiline treatment, 10 mg daily. Thereafter, the second FDOPA PET was performed for all subjects with a premedication administered 60 min before the PET imaging; one group received 10 mg of selegiline, and the other group received a single 400 mg dose of entacapone coadministered with 10 mg of selegiline. Selegiline treatment alone had no significant influence on striatal FDOPA metabolism. The FDOPA accumulation, expressed as striatal-to-occipital ratios and modified decarboxylation coefficients (k3R0), increased significantly after entacapone + selegiline administration in all subject populations. The FDOPA uptake rate constant (Ki) remained virtually unchanged in controls and in de novo patients but decreased significantly in levodopa-treated PD patients after entacapone + selegiline intake. Entacapone + selegiline administration did not influence significantly the unidirectional blood-to-brain clearance for FDOPA (K1D) or the relative dopadecarboxylase activity (k3D). The changes in the studied parameters after entacapone + selegiline administration probably reflect the effects of entacapone, since entacapone alone has caused similar changes in previous PET studies. Response in FDOPA accumulation to entacapone + selegiline was higher in controls and de novo patients compared with levodopa-treated PD patients. The milder response in levodopa-treated patients might reflect the reduced ability of the degenerated dopaminergic neurons to utilize the prolonged FDOPA availability, produced by entacapone. 相似文献
623.
ME Harper E Glynne-Jones L Goddard VJ Thurston K Griffiths 《Canadian Metallurgical Quarterly》1996,74(6):910-916
Vascular endothelial growth factor (VEGF) expression was examined by immunohistochemistry in 45 prostatic carcinoma specimens and ten benign prostatic tumours (BPH). The majority of carcinoma specimens exhibited cytoplasmic staining for VEGF and showed a trend of increasing expression with dedifferentiation (2p = 0.003). Immunoreactive VEGF was also seen in the prostatic carcinoma cell lines, the order of staining intensity was PC3 > DU145 > LNCaP. Intense granular cytoplasmic staining for VEGF was observed in neuroendocrine-like cells which were seen focally in many of the prostatic specimens. Consecutive sections were incubated with a chromogranin A antibody to confirm the neuroendocrine phenotype of these cells. A significant correlation (P < 0.0001) between the total number of intensely stained VEGF-positive cells and chromogranin A-positive cells was found. A subpopulation of neuroendocrine-like cells also showed intense immunoreactivity for transforming growth factor alpha (TGF-alpha). A correlation was observed (2p = 0.0092) between the intensity of VEGF and TGF-alpha immunostaining in carcinoma cells which were not of neuroendocrine differentiation. The presence of these two angiogenic factors may aid the neovascularisation of carcinomas and their increased expression in tumour-associated neuroendocrine cells may contribute to a more aggressive phenotype. 相似文献
624.
VJ Lowe JM Hoffman MW Hanson S Paine EW Massey LK Jordan L Gray RE Moon RE Coleman 《Canadian Metallurgical Quarterly》1994,21(2):103-113
Four statistical strategies were used to evaluate whether occurrence of daily stressors increases lower gastrointestinal (GI) symptoms in irritable bowel syndrome (IBS) patients. Across-subject concurrent correlations between weekly stress and symptoms were positive but casually ambiguous and obscured between- and within-subject and occasion relationships. Multiple regressions assessing (weekly and daily) relations showed that prior symptoms predicted subsequent symptoms but that prior and concurrent daily stress had no consistent effects. Idiographic correlations also showed little evidence for a relationship between stress and symptoms. Daily stress did not appear to increase GI symptoms in IBS patients on a general basis. Daily recording methodology, in conjunction with within-subject analytic strategies, is proposed as an innovative approach to examine relations between stress and physical symptomatology. 相似文献
625.
The letter describes a novel process for increasing the grain size in polycrystalline silicon films at temperatures near 500°C. This process, once perfected, could lead to mono-crystalline or large-grain, uniformly oriented polysilicon films on amorphous surfaces. 相似文献
626.
VJ Fernández-Pastor F Pérez JC García AM Diego F Guirado N Noguer 《Canadian Metallurgical Quarterly》1997,53(3):327-334
Two phenotypes of human influenza A(H1N1) virus are currently circulating in Japan. One (group 1) agglutinates both chicken and goose red blood cells (CRBC and GRBC), the other (group 2) agglutinates GRBC but not CRBC. In the 1995/6 season, group 2 viruses accounted for 70% of the H1N1 viruses isolated in MDCK cells. The 1995/6 viruses were located on two branches of the genetic tree. One branch contained both group 1 and group 2 viruses and the other branch contained only group 2 viruses. Group 2 viruses had aspartic acid at residue 225 in the haemagglutinin (HA) protein, the key amino acid residue for group 2 phenotype. The HA protein of group 1 viruses had a change from aspartic acid to asparagine at residue 225 and the expressed HA protein of these viruses adsorbed CRBC. Serial passage of group 2 viruses in MDCK cells or embryonated chicken eggs caused these viruses to gain the ability to agglutinate CRBC. MDCK-adapted viruses had the same amino acid sequences of HA polypeptide as the original ones, but egg-adapted viruses had changed amino acid sequences. The expressed HA protein from one egg-adapted virus that originally belonged to group 2 adsorbed CRBC. 相似文献
627.
The possibilities of discriminating between definite and indefinite (isodesmic) modes of self-association are explored by fitting the different models to stimulated data, using non-linear least-squares curve-fitting to determine the fitting parameters for real and impostor models. It was found that over an extensive range of values for the equilibrium constant of a non-ideal isodesmic generating model, only a non-ideal monomer-dimer-tetramer-octamer was a successful impostor model. Some criteria for rejecting inappropriate models are discussed. 相似文献
628.
Investigation of 4-transistor arrays in which the devices are very well matched at emitter currents above 100 nA has revealed correlation between burst noise and the departure from `matchness? at lower currents. A figure of merit based on the leakage currents ICBO,ICEO is introduced to compare individual devices and arrays. 相似文献
629.
630.