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61.
Abstract A diffraction grating has been manufactured in silica using interferometry and then replicated into perspex. Both grating profiles have then been characterized by fitting theory to experimentally obtained surface plasmon resonances excited on the grating surfaces after they had been coated with silver. The groove profile in the silica grating is distorted from purely sinusoidal. This distortion is very well characterized using the second-order surface plasmon and is described in this study a simple one-parameter model. The validity of the model is confirmed by similar examination of the surface plasmon resonances from the replica which is found to have the almost exactly the opposite distortion. 相似文献
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CK Combs DE Johnson SB Cannady TM Lehman GE Landreth 《Canadian Metallurgical Quarterly》1999,19(3):928-939
Microglial interaction with amyloid fibrils in the brains of Alzheimer's and prion disease patients results in the inflammatory activation of these cells. We observed that primary microglial cultures and the THP-1 monocytic cell line are stimulated by fibrillar beta-amyloid and prion peptides to activate identical tyrosine kinase-dependent inflammatory signal transduction cascades. The tyrosine kinases Lyn and Syk are activated by the fibrillar peptides and initiate a signaling cascade resulting in a transient release of intracellular calcium that results in the activation of classical PKC and the recently described calcium-sensitive tyrosine kinase PYK2. Activation of the MAP kinases ERK1 and ERK2 follows as a subsequent downstream signaling event. We demonstrate that PYK2 is positioned downstream of Lyn, Syk, and PKC. PKC is a necessary intermediate required for ERK activation. Importantly, the signaling response elicited by beta-amyloid and prion fibrils leads to the production of neurotoxic products. We have demonstrated in a tissue culture model that conditioned media from beta-amyloid- and prion-stimulated microglia or from THP-1 monocytes are neurotoxic to mouse cortical neurons. This toxicity can be ameliorated by treating THP-1 cells with specific enzyme inhibitors that target various components of the signal transduction pathway linked to the inflammatory responses. 相似文献
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CA McGibbon DE Krebs CA Trahan SB Trippel RW Mann 《Canadian Metallurgical Quarterly》1999,14(1):52-58
The mitochondrial, inner-membrane-associated, reversible NADPH-->NAD transhydrogenase of adult Hymenolepis diminuta physiologically couples matrix-localized, NADP-specific "malic" enzyme with NADH-dependent anaerobic electron transport. Employing submitochondrial particles (SMP) as the source of enzyme activity and both spectrophotometric and fluorometric assessments, the present study made evident that in its catalysis of transhydrogenation between NADPH and NAD, the cestode enzyme engages in the concomitant transmembrane translocation of protons. As assessed spectrophotometrically, the catalysis of NADPH-dependent NAD reduction by H. diminuta SMP was stimulated significantly by carbonyl cyanide 3-chlorophenylhydrazone (CCCP), carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP), as well as by the protonophoric anthelmintic, niclosamide. In addition, N,N'-dicyclohexylcarbodiimide (DCCD) markedly diminished SMP-catalyzed hydride ion transfer between NADPH and NAD. The catalysis by SMP of concomitant, transhydrogenase-mediated proton translocation was evaluated more directly via fluorometric assays using 8-anilino-1-napthalenesulfonic acid (ANS) as the probe. These latter evaluations revealed a transhydrogenase-dependent enhancement of ANS fluorescence in accord with an intravesicular accumulation of protons. ANS fluorescence was quenched rapidly when the assay system was supplemented with CCCP, FCCP, or niclosamide. Consistent with the helminth transhydrogenase acting as a proton pump, transhydrogenase-mediated enhanced fluorescence also was inhibited by DCCD. Considered collectively, these data indicated, apparently for the first time for any invertebrate system, that the transhydrogenase, in catalyzing the NADPH-->NAD reaction, acts in the translocation of protons from the matrix to the intermembrane space mitochondrial compartment. 相似文献
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P Mooney M Sarmiento JM Bishop N Biswas NM Cason L Dauwe J Godfrey VP Kenney R Pemper E Rojek RC Ruchti WD Shephard G Ginther RM Edelstein CP Forsyth K Gamarnik AE Kreymer RJ Lipton JM McQuade DM Potter JS Russ L Spiegel DE Johnson D Buchholz LM Cremaldi SW Delchamps HS Mao JL Rosen W Sakumoto RA Schluter SB Sontz C Winter 《Canadian Metallurgical Quarterly》1989,39(9):2494-2498
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Ten patients with newly diagnosed B-chronic lymphocytic leukaemia were treated with cladribin orally for five days every four weeks with a median of four series. This is the first reported clinical study where a purine analogue is administered orally. The tumour reducing effect was fast. Eight out of 10 patients responded with a partial or clinical complete remission. Two of these were in molecular biological complete remission. With an observation time of 22 months we have seen no serious side effects so far. A randomized study (including a long term follow up) between chlorambucil, fludarabin and cladribin is needed to clarify the future role of cladribin in B-CLL treatment. 相似文献
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