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991.
992.
Analogues of purine nucleosides and deoxynucleosides were tested for toxicity against the intraerythrocytic parasite Plasmodium falciparum in vitro culture. Sangivamycin (7-deaza-7-amido-adenosine) (IC37 of 0.3 microM), tubercidin (7-deaza-adenosine) (IC37 of 0.7 microM), 6-methylamino-deoxyadenosine (IC37 of 10 microM), 8-aza-2-amino-deoxy-adenosine (IC37 of 11 microM) and 2-chloro-adenosine (IC37 of 11 microM) were found to be the most toxic towards the parasite. Structure-activity analysis suggested that alteration of the purine ring at the 7 or 8 position significantly increased the toxicity of the compound against P. falciparum. Analysis by HPLC of parasite lysates which had been subjected to the cytotoxic compounds confirmed that alterations in the flux of the purine salvage pathways of the parasite had occurred. Comparison of the toxicity of these compounds against P. falciparum with the toxicity against a similar intraerythrocytic parasite, Babesia bovis, or human melanoma cell lines indicated a differential toxicity, in that many of the compounds toxic towards P. falciparum were relatively non-toxic towards human melanoma cell lines or B. bovis and vice versa. The mechanism of toxicity of the deoxyadenosine and adenosine analogues, whose normal metabolism involves transport, metabolism and incorporation into nucleic acids appears to vary significantly between P. falciparum, B. bovis and mammalian cells. 相似文献
993.
M Gar?on J Arvieux DH Beck EJ Beise A Boudard EB Cairns JM Cameron GW Dodson KA Dow M Farkhondeh HW Fielding JB Flanz R Goloskie S Hoibr?ten J Jourdan S Kowalski C Lapointe WJ McDonald B Nia LD Pham RP Redwine NL Rodning G Roy ME Schulze PA Souder J Soukup I The WE Turchinetz CF Williamson KE Wilson SA Wood W Ziegler 《Canadian Metallurgical Quarterly》1994,49(5):2516-2537
994.
L Fei AK Slade K Prasad M Malik WJ McKenna AJ Camm 《Canadian Metallurgical Quarterly》1995,26(2):472-480
OBJECTIVES: This study aimed to assess autonomic nervous system activity in patients with hypertrophic cardiomyopathy. BACKGROUND: Patients with hypertrophic cardiomyopathy are traditionally thought to have increased sympathetic activity. However, convincing evidence is lacking. METHODS: Heart rate variability was assessed from 24-h ambulatory electrocardiographic (Holter) recordings in 31 patients with hypertrophic cardiomyopathy and 31 age- and gender-matched normal control subjects in a drug-free state. Spectral heart rate variability was calculated as total (0.01 to 1.00 Hz), low (0.04 to 0.15 Hz) and high (0.15 to 0.40 Hz) frequency components using fast Fourier transformation analysis. RESULTS: There was a nonsignificant decrease in the total frequency component of heart rate variability in patients with hypertrophic cardiomyopathy compared with that of normal subjects (mean +/- SD 7.24 +/- 0.88 versus 7.59 +/- 0.57 ln[ms2], p = 0.072). Although there was no significant difference in the high frequency component (5.31 +/- 1.14 versus 5.40 +/- 0.91 ln[ms2], p = 0.730), the low frequency component was significantly lower in patients than in normal subjects (6.25 +/- 1.00 versus 6.72 +/- 0.61 ln[ms2], p = 0.026). After normalization (i.e., division by the total frequency component values), the low frequency component was significantly decreased (38 +/- 8% versus 43 +/- 8%, p = 0.018) and the high frequency component significantly increased (16 +/- 6% versus 12 +/- 6%, p = 0.030) in patients with hypertrophic cardiomyopathy. The low/high frequency component ratio was significantly lower in these patients (0.94 +/- 0.64 versus 1.33 +/- 0.55, p = 0.013). In patients with hypertrophic cardiomyopathy, heart rate variability was significantly related to left ventricular end-systolic dimension and left atrial dimension but not to maximal left ventricular wall thickness. No significant difference in heart rate variability was found between 14 victims of sudden cardiac death and 10 age- and gender-matched low risk patients. CONCLUSIONS: Our observations suggest that during normal daily activities, patients with hypertrophic cardiomyopathy experience a significant autonomic alteration with decreased sympathetic tone. 相似文献
995.
ER van der Vorm A Kuipers JW Bonenkamp WJ Kleijer L Van Maldergem J Herwig JA Maassen 《Canadian Metallurgical Quarterly》1993,36(2):172-174
Lipodystrophic diabetes mellitus of the Seip-Berardinelli type is a syndrome associated with insulin resistance and recessive inheritance. We have examined whether mutations in the insulin receptor are pathogenetic factors in this syndrome. Fibroblasts from three different patients with Seip-Berardinelli's lipodystrophy were tested for insulin binding, and insulin-stimulated receptor autophosphorylation. In addition, the coding region of both alleles of the iinsulin receptor gene was sequenced. No abnormalities in the number of high affinity insulin binding sites, and insulin-stimulated receptor autophosphorylation were detected. The insulin receptor related insulin-like growth factor I receptor also showed no functional changes. DNA sequence analysis of the amplified exons of the insulin receptor gene showed a silent mutation in patient 1 at codon Ser339, changing AGT to AGC. In patient 2 a heterozygous Met for Val substitution at position 985 was detected, which is a rare polymorphism. In patient 3 no mutations, other than described polymorphisms, were observed. These findings demonstrate that the primary genetic lesion in Seip-Berardinelli's lipodystrophy is outside the insulin receptor gene and that an involvement of the insulin-like growth factor I receptor is also unlikely. 相似文献
996.
997.
We present a patient with transient global amnesia (TGA) whose diffusion-weighted MRI (DWI) showed increased signal in the splenium of the corpus callosum and in the left parahippocampal gyrus. The absence of high signal on the corresponding apparent diffusion coefficient (ADC) images supports the diagnosis of an acute infarction. This finding provides a temporal relation between cerebral ischemia and infarction in the territory of posterior cerebral artery and in certain cases of TGA. An early means of detecting ischemia in TGA by DWI may influence clinical decisions made in patient evaluation and management. 相似文献
998.
JD Eudy MD Weston S Yao DM Hoover HL Rehm M Ma-Edmonds D Yan I Ahmad JJ Cheng C Ayuso C Cremers S Davenport C Moller CB Talmadge KW Beisel M Tamayo CC Morton A Swaroop WJ Kimberling J Sumegi 《Canadian Metallurgical Quarterly》1998,280(5370):1753-1757
Usher syndrome type IIa (OMIM 276901), an autosomal recessive disorder characterized by moderate to severe sensorineural hearing loss and progressive retinitis pigmentosa, maps to the long arm of human chromosome 1q41 between markers AFM268ZD1 and AFM144XF2. Three biologically important mutations in Usher syndrome type IIa patients were identified in a gene (USH2A) isolated from this critical region. The USH2A gene encodes a protein with a predicted size of 171.5 kilodaltons that has laminin epidermal growth factor and fibronectin type III motifs; these motifs are most commonly observed in proteins comprising components of the basal lamina and extracellular matrixes and in cell adhesion molecules. 相似文献
999.
1000.
The pentaacetate esters of selected hexoses were recently found to stimulate insulin release. The kinetics of their hydrolysis was now investigated in both rat pancreatic islet homogenates and intact islets. In islet homogenates, the hydrolysis of alpha-d-glucose pentaacetate, as judged from the measurement of acetate production, displayed a pH optimum of 7.4 and a Km for the ester of 0.95 mM. At pH 7.4, the reaction velocity was about 5 times higher than the rate of alpha-d-glucose pentaacetate hydrolysis by intact islets, as judged from the ester-induced increase in the acetate content of both the islet and surrounding incubation medium. Comparable results were obtained in intact islets exposed to either beta-l-glucose pentaacetate or beta-d-galactose pentaacetate. The ester content of the islets after 120 min incubation was close to 0.1 nmol/islet, yielding an apparent intracellular concentration at least one order of magnitude higher than the extracellular concentration (1.7 mM). These findings indicate that hexose esters that either stimulate insulin release or fail to do so are equally well taken up and hydrolyzed by islet cells. They are compatible, therefore, with the view that the insulinotropic action of some of these esters may be favored by the catabolism of their hexose moiety, although some other mechanisms for stimulation of insulin release must be operative in the case of beta-l-glucose pentaacetate. 相似文献