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1.
2.
Jun Ogata Kentaro Hirao Kenya Nishioka Arisa Hayashida Yuanzhe Li Hiroyo Yoshino Soichiro Shimizu Nobutaka Hattori Yuzuru Imai 《International journal of molecular sciences》2021,22(7)
Leucine-rich repeat kinase 2 (LRRK2) is a major causative gene of late-onset familial Parkinson’s disease (PD). The suppression of kinase activity is believed to confer neuroprotection, as most pathogenic variants of LRRK2 associated with PD exhibit increased kinase activity. We herein report a novel LRRK2 variant—p.G2294R—located in the WD40 domain, detected through targeted gene-panel screening in a patient with familial PD. The proband showed late-onset Parkinsonism with dysautonomia and a good response to levodopa, without cognitive decline or psychosis. Cultured cell experiments revealed that p.G2294R is highly destabilized at the protein level. The LRRK2 p.G2294R protein expression was upregulated in the patient’s peripheral blood lymphocytes. However, macrophages differentiated from the same peripheral blood showed decreased LRRK2 protein levels. Moreover, our experiment indicated reduced phagocytic activity in the pathogenic yeasts and α-synuclein fibrils. This PD case presents an example wherein the decrease in LRRK2 activity did not act in a neuroprotective manner. Further investigations are needed in order to elucidate the relationship between LRRK2 expression in the central nervous system and the pathogenesis caused by altered LRRK2 activity. 相似文献
3.
Akiko Suzuki Mina Minamide Chihiro Iwaya Kenichi Ogata Junichi Iwata 《International journal of molecular sciences》2020,21(23)
Carbohydrates, fats, and proteins are the underlying energy sources for animals and are catabolized through specific biochemical cascades involving numerous enzymes. The catabolites and metabolites in these metabolic pathways are crucial for many cellular functions; therefore, an imbalance and/or dysregulation of these pathways causes cellular dysfunction, resulting in various metabolic diseases. Bone, a highly mineralized organ that serves as a skeleton of the body, undergoes continuous active turnover, which is required for the maintenance of healthy bony components through the deposition and resorption of bone matrix and minerals. This highly coordinated event is regulated throughout life by bone cells such as osteoblasts, osteoclasts, and osteocytes, and requires synchronized activities from different metabolic pathways. Here, we aim to provide a comprehensive review of the cellular metabolism involved in bone development and homeostasis, as revealed by mouse genetic studies. 相似文献
4.
Tetsuya Nanba Shouichi Masukawa Atsushi Ogata Junko Uchisawa Akira Obuchi 《Applied catalysis. B, Environmental》2005,61(3-4):288-296
The catalytic decomposition of acrylonitrile (AN) over Cu-ZSM-5 prepared with various Cu loadings was investigated. AN conversion, during which the nitrogen atoms in AN were mainly converted to N2, increased as Cu loading increased. N2 selectivities as high as 90–95% were attained. X-ray diffraction measurements (XRD) and temperature-programmed reduction by H2 (H2-TPR) showed the existence of bulk CuO in Cu-ZSM-5 with a Cu loading of 6.4 wt% and the existence of highly dispersed CuO in Cu-ZSM-5 with a Cu loading of 3.3 wt%. Electron spin resonance measurements revealed that Cu-ZSM-5 contains three forms of isolated Cu2+ ions (square-planar, square-pyramidal, and distorted square-pyramidal). The H2-TPR results suggested that in Cu-ZSM-5 with a Cu loading of 2.9 wt% and below, Cu+ existed even after oxidizing pretreatment. The activity of AN decomposition over Cu/SiO2 suggested that CuO could form N2, but, independent of the CuO dispersion, nitrogen oxides (NOx) were formed above 350 °C. Cu+ and the square-pyramidal and distorted square-pyramidal forms of Cu2+ showed low activity for AN decomposition. Temperature-programmed desorption of NH3 suggested that N2 formation from NH3 proceeded on Cu2+, resulting in the formation of Cu+. The Cu+ ions were oxidized to Cu2+ at around 300 °C. Thus, high N2 selectivity over Cu-ZSM-5 with a wide range of temperature was probably attained by the reaction over the square-planar Cu2+, which can be reversibly reduced and oxidized. 相似文献
5.
The inhibitory effect of alpha-tocopherol on methemoglobin formation in normal and acatalasemic mice was studied by exposing their hemolysates to nitric oxide. Methemoglobin formation in normal and acatalasemic mouse hemolysates exposed to nitric oxide were significantly inhibited by the addition of alpha-tocopherol at final concentrations ranging from 1.2 to 5.8 mM. Negative correlations were observed between the logarithm of alpha-tocopherol concentration and the methemoglobin formation. The formation of methemoglobin in acatalasemic mouse hemolysates was greater than that in normal mouse hemolysates with or without added alpha-tocopherol. The methemoglobin formation in acatalasemic mice was also significantly inhibited by addition of more than 500 units/ml of catalase, and the methemoglobin formation in normal and acatalasemic mice was also inhibited with sodium diethyldithiocarbamate at a final concentration of 1 M. 相似文献
6.
Jefferson Fabrício Cardoso Lins Hugo Ricardo Z. Sandim Hans-Jürgen Kestenbach 《Journal of Materials Science》2007,42(16):6572-6577
The present paper reports the experimental results on the microstructural and textural characterization of a hot-rolled IF
steel. The IF steel was hot-rolled in multiple passes in the austenitic field (1,070 °C) followed by air-cooling. SEM, TEM,
and LOM were used to image the microstructure of the material. The global texture was determined by X-ray diffraction (XRD)
technique. The mesotexture of selected regions was investigated by electron backscatter diffraction (EBSD). Results show the
presence of a diffuse (nearly random) and weak texture in the hot-band that consists of recrystallized polygonal grains and
subgrains. The fraction of boundaries with misorientations comprised in the interval 2° ≤ ψ < 15° was found to be lower than
5%. It can be concluded that these low angle boundaries and the presence of subgrains can be associated to the existence of
a few areas softened by recovery during or after hot rolling in austenitic field. 相似文献
7.
S Fukumoto M Suzawa Y Takeuchi Y Kodama K Nakayama E Ogata T Matsumoto T Fujita 《Canadian Metallurgical Quarterly》1996,81(7):2554-2558
8.
An intrinsic guanine nucleotide exchange inhibitor in Gi2 alpha. Significance of G-protein self-suppression which antagonizes receptor signal 总被引:1,自引:0,他引:1
T Okamoto Y Murayama SM Strittmatter T Katada S Asano E Ogata I Nishimoto 《Canadian Metallurgical Quarterly》1994,269(19):13756-13759
The alpha subunit of Gi2 (Gi2 alpha) is a member of the heterotrimeric G protein family, which transduces receptor signals as a proto-oncogene product. We have found a novel self-suppressive region in Gi2 alpha near its C terminus. A polypeptide consisting of residues 338-352 of Gi2 alpha (Gi2 alpha-339-352) antagonizes receptor- and receptor peptide-stimulated Gi2 alpha activation, without affecting basal activity. Antagonism by Gi2 alpha-338-352 is attributable to an interaction with activated Gi2 alpha, which is not competitive with receptor polypeptides. Combined with the reports suggesting the presence of self-suppressive domains in a juxta-C-terminal portion of Gi2 alpha and G(o) alpha, this study supports the hypothesis that Gi2 alpha-338-352 constitutes an intrinsic guanine nucleotide exchange inhibitor, which in turn antagonizes receptor stimulation, suggesting that G proteins are activated by receptors through relaxation of a self-suppressive conformation. 相似文献
9.
To estimate the response to hormone replacement therapy (HRT) by bone metabolic markers, 36 patients with postmenopausal osteoporosis or osteopenia were studied to assess the correlation between percent baseline changes in lumbar bone mineral density (BMD) after 12 months and those in various bone metabolic markers after 3, 6, and 12 months of HRT. All the patients were treated with 0.625 mg of conjugated estrogen and 2.5 mg of medroxyprogesterone per day and continued for 12 months. BMD was significantly increased up to 4.19 +/- 0.87% after 6 months and 4.93 +/- 1.27% after 12 months of HRT (p = 0.0001 by analysis of variance). In accordance with this, changes in the levels of osteocalcin (p = 0.041), alkaline phosphatase (p = 0.0001), N-terminal osteocalcin (p = 0.0001), urinary excretion of pyridinoline/Cr (p = 0.0001), and deoxypyridinoline/Cr (p = 0.0001) were significantly decreased, respectively. Among these bone metabolic markers, only the change in the serum N-terminal osteocalcin at 3 months (r = 0.557, p = 0.0022), at 6 months (r = 0.470, p = 0.0184), and at 12 months (r = 0.545, p = 0.0061) significantly correlated with the change in BMD 12 months after HRT. The elution profiles of immunoreactive osteocalcin-related molecules in serum fractionated by reverse-phase high performance liquid chromatography revealed that the N-terminal fragment as well as the intact osteocalcin molecule decreased after 3 months of HRT. These results demonstrate that N-terminal osteocalcin is a suitable predictor for estimating good responders to HRT in postmenopausal women. 相似文献
10.