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121.
Sagar Chaki Edmund Clarke Natasha Sharygina Nishant Sinha 《Formal Methods in System Design》2008,32(3):235-266
This paper presents an automated and compositional procedure to solve the substitutability problem in the context of evolving software systems. Our solution contributes two
techniques for checking correctness of software upgrades: (1) a technique based on simultaneous use of over-and under-approximations
obtained via existential and universal abstractions; (2) a dynamic assume-guarantee reasoning algorithm—previously generated component assumptions are reused and altered on-the-fly to prove
or disprove the global safety properties on the updated system. When upgrades are found to be non-substitutable, our solution
generates constructive feedback to developers showing how to improve the components. The substitutability approach has been
implemented and validated in the ComFoRT reasoning framework, and we report encouraging results on an industrial benchmark.
This is an extended version of a paper, Dynamic Component Substitutability Analysis, published in the Proceedings of the Formal Methods 2005 Conference, Lecture Notes in Computer Science, vol. 3582, by the
same authors. This research was sponsored by the National Science Foundation under grant nos. CNS-0411152, CCF-0429120, CCR-0121547,
and CCR-0098072, the Semiconductor Research Corporation under grant no. TJ-1366, the US Army Research Office under grant no.
DAAD19-01-1-0485, the Office of Naval Research under grant no. N00014-01-1-0796, the ICAST project and the Predictable Assembly
from Certifiable Components (PACC) initiative at the Software Engineering Institute, Carnegie Mellon University. The views
and conclusions contained in this document are those of the authors and should not be interpreted as representing the official
policies, either expressed or implied, of any sponsoring institution, the US government or any other entity. 相似文献
122.
Stella Clarke Gerhard Schillhuber Michael F. Zaeh Heinz Ulbrich 《Multimedia Systems》2008,13(4):253-261
The remote nature of telepresence scenarios can be seen as a strongpoint and also as a weakness. Although it enables the remote
control of robots in dangerous or inaccessible environments, it necessarily involves some kind of communication mechanism
for the transmission of control signals. This communication mechanism necessarily involves adverse network effects such as
delay. Three mechanisms aimed at improving the effects of network delay are presented in this paper: (1) Motion prediction
to partially compensate for network delays, (2) force prediction to learn a local force model, thereby reducing dependency
on delayed force signals, and (3) haptic data compression to reduce the required bandwidth of high frequency data. The utilized
motion prediction scheme was shown to improve operator performance, but had no influence on operator immersion. The force
prediction provided haptic feedback through synchronous forces from the local model, thereby stabilizing the control loop.
The developed haptic data compression scheme reduced the number of packets sent across the network by 90%, while improving
the quality of the haptic feedback. 相似文献
123.
RM Meffert 《Canadian Metallurgical Quarterly》1994,73(3):22-4; quiz 25
Due to the pathologic nature of oral bacteria, the partially edentulous implant patient is at a greater risk than the fully edentulous. Peri-implantitis and/or retrograde peri-implantitis can result in ultimate loss of the implant fixture. It is important that the implant dentist understand the difference between the ailing implant, the failing implant, and the failed implant. This article discusses the pathologic diseases that affect dental implants and how to treat the "infected" implant (degranulation and detoxification) for titanium and hydroxylapatite-coated implants. Implant maintenance, including hand or motorized brushes, flosses, and oral rinses (chlorhexidine, 0.2%) will also be presented. 相似文献
124.
M Inada RM Crowl AC Bekkers H Verheij J Weiss 《Canadian Metallurgical Quarterly》1994,269(42):26338-26343
It has been suggested (Kini, R. R., and Evans, H. J. (1987) J. Biol. Chem. 262, 14402-14407) that the anticoagulant activity of members of the 14-kDa phospholipase A2 (PLA2) family depends on the presence of basic residues within a variable surface region (residues 54-77) distinct from both the conserved catalytic machinery and surface sites mediating the antibacterial action of these enzymes (see Weiss, J., Inada, M., Elsbach, P., and Crowl, R. M. (1994) J. Biol. Chem. 269, 26331-26337). To further define the determinants of the anticoagulant activity of PLA2, we have analyzed the inhibitory effects of purified native and recombinant PLA2 on cell-free prothrombinase. Both native and recombinant wild-type pig pancreas (net charge -1) and human "secretory" PLA2 (net charge +15) produced similar dose-dependent inhibition of prothrombinase activity that was significantly less potent than a toxic PLA2 purified from snake venom. Site-specific mutations that either increased or decreased PLA2 activity toward bactericidal/permeability-increasing protein-treated Escherichia coli by up to 50-fold had no effect on antiprothrombinase activity. In contrast, substitution of Arg for Asp-59/Gly for Ser-60 in the pig PLA2 increased antiprothrombinase activity by 5-10-fold without affecting catalytic activity toward a range of phospholipid substrates or antibacterial activity. Comparison of antiprothrombinase activity of catalytically active and inactive forms of the PLA2 and under a range of phospholipid conditions revealed that the potent antiprothrombinase activity of native toxic venom PLA2 and of the D59R.S60G mutant pancreatic PLA2 reflect combined catalytic and noncatalytic actions, the latter apparently dependent on basic residues at discrete surface sites in the enzyme. 相似文献
125.
RT Malison LH Price R Berman CH van Dyck GH Pelton L Carpenter G Sanacora MJ Owens CB Nemeroff N Rajeevan RM Baldwin JP Seibyl RB Innis DS Charney 《Canadian Metallurgical Quarterly》1998,44(11):1090-1098
BACKGROUND: Prior research has suggested reductions in the density of serotonin transporter (SERT) binding sites in blood platelets and post-mortem brain tissue of depressed patients. We sought to determine whether patients with unipolar major depression have diminished SERT availability as assessed by both brainstem [123I] beta-CIT SPECT and platelet [3H]paroxetine binding. METHODS: Drug-free depressed and healthy subjects were injected with 211 +/- 22 MBq [123I] beta-CIT and imaged 24 +/- 2 h later under equilibrium conditions. A ratio of specific to nonspecific brain uptake (V3" = (brainstem-occipital)/occipital), a measure proportional to the binding potential (Bmax/Kd), was used for all comparisons. RESULTS: Results showed a statistically significant reduction in brainstem V3" values in depressed as compared to healthy subjects (3.1 +/- .9 vs. 3.8 +/- .8, p = .02). Platelet [3H]paroxetine binding was not altered (Bmax = 2389 +/- 484 vs. 2415 +/- 538 fmol/mg protein, p = .91) and was not significantly correlated with brainstem [123I] beta-CIT binding (r = -0.14, p = .48). CONCLUSIONS: These data are the first to suggest reductions in the density of brain SERT binding sites in living depressed patients. These findings provide further support for a preeminent role for alterations in serotonergic neurons in the pathophysiology of depression. 相似文献
126.
Rigid body rotation of five domains and movements within their interfacial joints provide a rational context for understanding why HIV protease mutations that arise in drug resistant strains are often spatially removed from the drug or substrate binding sites. Domain motions associated with substrate binding in the retroviral HIV-1 and SIV proteases are identified and characterized. These motions are in addition to closure of the flaps and result from rotations of approximately 6-7 degrees at primarily hydrophobic interfaces. A crystal structure of unliganded SIV protease (incorporating the point mutation Ser 4 His to stabilize the protease against autolysis) was determined to 2.0 A resolution in a new space group, P3221. The structure is in the most "open" conformation of any retroviral protease so far examined, with six residues of the flaps disordered. Comparison of this and unliganded HIV structures, with their respective liganded structures by difference distance matrixes identifies five domains of the protease dimer that move as rigid bodies against one another: one terminal domain encompassing the N- and C-terminal beta sheet of the dimer, two core domains containing the catalytic aspartic acids, and two flap domains. The two core domains rotate toward each other on substrate binding, reshaping the binding pocket. We therefore show that, for enzymes, mutations at interdomain interfaces that favor the unliganded form of the target active site will increase the off-rate of the inhibitor, allowing the substrate greater access for catalysis. This offers a mechanism of resistance to competitive inhibitors, especially when the forward enzymatic reaction rate exceeds the rate of substrate dissociation. 相似文献
127.
CA Caldarone HK Najm M Kadletz JF Smallhorn RM Freedom WG Williams JG Coles 《Canadian Metallurgical Quarterly》1998,66(5):1521-1526
BACKGROUND: Recent reports have cited improving results for surgical management of isolated total anomalous pulmonary venous drainage. Complex cases (with other cardiac anomalies) are less frequently reported and are associated with higher mortality. METHODS: Retrospective review identified 170 consecutive patients treated for total anomalous pulmonary venous drainage from 1982 to 1996: 44 cases were "complex" (with significant associated cardiac lesions) and 126 cases were "simple." RESULTS: Operative mortality for simple cases decreased from 26% to 8%, and mortality for complex cases remained constant at 52%. Age, size, and the presence of atrial isomerism were univariate predictors of mortality. Multivariable analysis identified only univentricular hearts and associated cardiac lesions as predictors of operative mortality. Pulmonary artery (n = 16) and arteriopulmonary (n = 7) shunting strategies for complex cases resulted in less than 30% long-term survival. CONCLUSIONS: Despite improvement in survival for simple cases, management of total anomalous pulmonary venous drainage with single-ventricle hearts or other associated cardiac lesions remains problematic. 相似文献
128.
129.
Structural intermediates occurring in the photocycle of wild-type bacteriorhodopsin are trapped by illuminating hydrated, glucose-embedded purple membrane at 170 K, 220 K, 230 K, and 240 K. We characterize light-induced changes in protein conformation by electron diffraction difference Fourier maps, and relate these to previous work on photocycle intermediates by infrared (FTIR) spectroscopy. Samples illuminated at 170 K are confirmed by FTIR spectroscopy to be in the L state; a difference Fourier projection map shows no structural change within the 0.35-nm resolution limit of our data. Difference maps obtained with samples illuminated at 220 K, 230 K, and 240 K, respectively, reveal a progressively larger structural response in helix F when the protein is still in the M state, as judged by the FTIR spectra. Consistent with previous structural studies, an adjustment in the position or in the degree of ordering of helix G accompanies this motion. The model of the photocycle emerging from this and previous studies is that bacteriorhodopsin experiences minimal change in protein structure until a proton is transferred from the Schiff base to Asp85. The M intermediate then undergoes a conformational evolution that opens a hydrated "half-channel," allowing the subsequent reprotonation of the Schiff base by Asp96. 相似文献
130.
Pancreatic cancer is a highly aggressive and treatment-refractory cancer. A clinically-relevant animal model is necessary to develop therapy for metastatic pancreatic cancer. In this study we evaluated the efficacy of mitomycin C (MMC) and 5-FU against the human pancreatic adenocarcinoma cell line PAN-12 in an orthotopic human metastatic pancreatic cancer nude mice model. The model is constructed by surgical orthotopic implantation (SOI) of histologically intact tumor tissue in the tail portion of the pancreas near the spleen. PAN-12 grew very aggressively in the control group of nude mice with extensive local invasion and distant metastasis to various organs with a propensity for the lung but to other organs as well, including the liver, kidney and regional and distant lymph nodes. In a striking effect none of the mice in the MMC-treated group developed tumor. Although mice in the 5-FU treated group survived statistically significantly longer than those in the untreated control, the overall incidence of metastasis in these mice was equivalent to those in the control. However no liver or kidney metastases were found in the 5-FU treated animals perhaps accounting in part for their longer survival. This "clinical" nude mouse model of highly metastatic pancreatic cancer can now be used to discover new effective agents for this disease. 相似文献