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排序方式: 共有1069条查询结果,搜索用时 15 毫秒
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Filippo Lococo Massimiliano Paci Cristian Rapicetta Teresa Rossi Valentina Sancisi Luca Braglia Silvio Cavuto Alessandra Bisagni Italia Bongarzone Douglas M. Noonan Adriana Albini Sally Maramotti 《International journal of molecular sciences》2015,16(8):19612-19630
Assessment of biological diagnostic factors providing clinically-relevant information to guide physician decision-making are still needed for diseases with poor outcomes, such as non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a promising molecule in the clinical management of NSCLC. While the EGFR transmembrane form has been extensively investigated in large clinical trials, the soluble, circulating EGFR isoform (sEGFR), which may have a potential clinical use, has rarely been considered. This study investigates the use of sEGFR as a potential diagnostic biomarker for NSCLC and also characterizes the biological function of sEGFR to clarify the molecular mechanisms involved in the course of action of this protein. Plasma sEGFR levels from a heterogeneous cohort of 37 non-advanced NSCLC patients and 54 healthy subjects were analyzed by using an enzyme-linked immunosorbent assay. The biological function of sEGFR was analyzed in vitro using NSCLC cell lines, investigating effects on cell proliferation and migration. We found that plasma sEGFR was significantly decreased in the NSCLC patient group as compared to the control group (median value: 48.6 vs. 55.6 ng/mL respectively; p = 0.0002). Moreover, we demonstrated that sEGFR inhibits growth and migration of NSCLC cells in vitro through molecular mechanisms that included perturbation of EGF/EGFR cell signaling and holoreceptor internalization. These data show that sEGFR is a potential circulating biomarker with a physiological protective role, providing a first approach to the functional role of the soluble isoform of EGFR. However, the impact of these data on daily clinical practice needs to be further investigated in larger prospective studies. 相似文献
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W. F. Flanagan Lijun Zhong B. D. Lichter 《Metallurgical and Materials Transactions A》1993,24(3):553-559
A model is proposed to explain transgranular-stress corrosion cracking (T-SCC) in face-centered cubic (fcc) materials. Crack
propagation is shown to be anisotropic, in that growth near {110} < 001> is discontinuous due to crack arrest by dislocation
blunting whereas growth away from this growth orientation is continuous. For the former case, renucleation of arrested cracks
involves active dissolution of shear bands at the crack tip, which changes the stress state at Lomer-Cottrell locks, causing
them to fail by cleavage. Once the crack is nucleated, its instantaneous macroscopic crack-growth velocity is considered to
be comprised of multiple nucleation of microcracks with intervening arrests. This microcracking results from the interaction
of the stress fields from neighboring cracks which are forming simultaneously, the crack-opening constraint due to ligaments
which act as “bridges” behind the crack front, and the localized dissolution at the microcrack tip which affectsK
IC and leads to the “cobblestone” appearance. Experimental evidence and theoretical considerations are presented to support
the model. The system studied was Cu-25 at. pct Au in 0.6 M NaCl solution at potentials between 300 and 400 mV (sce), which
precludes hydrogen embrittlement.
This article is based on a presentation made in the symposium “Quasi-Brittle Fracture” presented during the TMS fall meeting,
Cincinnati, OH, October 21–24, 1991, under the auspices of the TMS Mechanical Metallurgy Committee and the ASM/MSD Flow and
Fracture Committee. 相似文献
5.
Modelling of effects of ultrastructural morphology on the hygroelastic properties of wood fibres 总被引:1,自引:0,他引:1
Wood fibres constitute the structural framework of e.g. wood, paper, board and composites, where stiffness and dimensional
stability are of importance. An analytical modelling approach has been used for prediction of hygroelastic response, and assessment
of the stresses in thick-walled cylinder models of wood fibres. A wood fibre was idealised as a multilayered hollow cylinder
made of orthotropic material with helical orientation. The hygroelastic response of the layered assembly due to axisymmetric
loading and moisture content changes was obtained by solving the corresponding boundary value problem of elasticity. A simple
solution scheme based on the state space approach and the transfer matrix method was employed. This was combined with an analytical
ultrastructural homogenisation method, used to link hygroelastic properties of constituent wood polymers to properties of
each layer. Predicted hygroelastic response captured experimentally measured behaviour. Fibres that were constrained not to
twist showed a stiffer response than fibres allowed twisting under uniaxial loading. It was also shown that the ultrastructure,
i.e. the microfibril angle, will control the hygroexpansion in the same way as it controls the compliance of the cell wall.
Qualitative failure trends comparable with experimental observations could be established with stress analysis and a simple
plane-stress failure criterion. 相似文献
6.
Maykel Cruz-Monteagudo Cristian Robert Munteanu Fernanda Borges Eugenio Uriarte Humberto González-Díaz 《Polymer》2008,49(25):5575-5587
The Quantitative Structure-Property Relationships (QSPRs) based on Graph or Network Theory are important for predicting the properties of polymeric systems. In the three previous papers of this series (Polymer 45 (2004) 3845-3853; Polymer 46 (2005) 2791-2798; and Polymer 46 (2005) 6461-6473) we focused on the uses of molecular graph parameters called topological indices (TIs) to link the structure of polymers with their biological properties. However, there has been little effort to extend these TIs to the study of complex mixtures of artificial polymers or biopolymers such as nucleic acids and proteins. In this sense, Blood Proteome (BP) is one of the most important and complex mixtures containing protein polymers. For instance, outcomes obtained by Mass Spectrometry (MS) analysis of BP are very useful for the early detection of diseases and drug-induced toxicities. Here, we use two Spiral and Star Network representations of the MS outcomes and defined a new type of TIs. The new TIs introduced here are the spectral moments (πk) of the stochastic matrix associated to the Spiral graph and describe non-linear relationships between the different regions of the MS characteristic of BP. We used the MARCH-INSIDE approach to calculate the πk(SN) of different BP samples and S2SNet to determine several Star graph TIs. In the second step, we develop the corresponding Quantitative Proteome-Property Relationship (QPPR) models using the Linear Discriminant Analysis (LDA). QPPRs are the analogues of QSPRs in the case of complex biopolymer mixtures. Specifically, the new QPPRs derived here may be used to detect drug-induced cardiac toxicities from BP samples. Different Machine Learning classification algorithms were used to fit the QPPRs based on πk(SN), showing J48 decision tree classifier to have the best performance. These results suggest that the present approach captures important features of the complex biopolymers mixtures and opens new opportunities to the application of the idea supporting classic QSPRs in polymer sciences. 相似文献
7.
N.W. Alnaser R. Flanagan S.E. Al-Khalifa R. Mumtaz S. El-Masri W.E. Alnaser 《Building and Environment》2007
The Bahrain International Circuit (BIC) is considered as one of the best international racing car track in terms of technical aspects and architectural quality. Two Formula 1 races have been hosted in the Kingdom of Bahrain, in 2004 and 2005, at BIC. The BIC had recently won the award of the best international racing car circuit. 相似文献
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JM Flanagan M Kataoka T Fujisawa DM Engelman 《Canadian Metallurgical Quarterly》1993,32(39):10359-10370
Deletion of 13 amino acids from the carboxyl terminus of staphylococcal nuclease (WTSNase delta) results in a denatured, partially unfolded molecule that lacks significant persistent secondary structure but is relatively compact and monomeric under physiological conditions [Shortle & Meeker (1989) Biochemistry 28, 936-944; Flanagan et al. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 748-752]. Because of these and other properties of the SNase delta polypeptide, it is a useful model system for investigating the conformation of the denatured state of a protein without using extreme temperature or solvent conditions. Moreover, since the modification is a carboxyl-terminal deletion, SNase delta may also resemble a transient state of the polypeptide chain as it emerges from a ribosome prior to its folding. In the present study, we have examined the sizes and conformations of mutated forms of SNase delta, using small-angle X-ray scattering and circular dichroism spectroscopy. Seven mutated forms were studied: four with single substitutions, two with double substitutions, and one triple substitution. When present in the full-length SNase, each of these mutated forms exhibited unusual behavior upon solvent or thermal denaturation. In the case of the truncated form (SNase delta), the small-angle scattering curves of the mutated forms fall into two classes: one resembling the scattering curve of compact native nuclease and the other having features consistent with those expected for an expanded coil-like polymer. In contrast, the scattering curve of WT SNase delta exhibits features intermediate between those observed for globular proteins and random polymers. The amino acid substitutions that gave rise to compact, native-like versions of SNase delta were all of the m--type (m-substitutions are predicted to decrease the size of the denatured state). Those which gave rise to versions of SNase delta that were more extended and coil-like than WT SNase delta were of the m+ type (m+ substitutions are predicted to increase the size of the denatured state). Estimates of the residual secondary structure present in WT SNase delta, as well as both the m+ and m-substituted versions of SNase delta, as determined by CD, suggest that the formation of secondary structure and compaction of the polypeptide chain occur concurrently. Our results show that single amino acid substitutions can radically alter the conformational distribution of a partially condensed polypeptide chain.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
10.