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排序方式: 共有1295条查询结果,搜索用时 12 毫秒
31.
Dr. Maria L. Di Paolo Dr. Michael S. Christodoulou Dr. Alessandra M. Calogero Dr. Luca Pinzi Prof. Giulio Rastelli Prof. Daniele Passarella Prof. Graziella Cappelletti Prof. Lisa Dalla Via 《ChemMedChem》2019,14(18):1641-1652
A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (Ki) values in the sub-micromolar range and a good selectivity index (Ki MAO-A/Ki MAO-B>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity. 相似文献
32.
Camara N Jouault B Jabakhanji B Caboni A Tiberj A Consejo C Godignon P Camassel J 《Nanoscale research letters》2011,6(1):141
Using high-temperature annealing conditions with a graphite cap covering the C-face of, both, on axis and 8° off-axis 4H-SiC
samples, large and homogeneous single epitaxial graphene layers have been grown. Raman spectroscopy shows evidence of the
almost free-standing character of these monolayer graphene sheets, which was confirmed by magneto-transport measurements.
On the best samples, we find a moderate p-type doping, a high-carrier mobility and resolve the half-integer quantum Hall effect typical of high-quality graphene samples.
A rough estimation of the density of states is given from temperature measurements. 相似文献
33.
Herein we propose the D ‐Trp‐Phe sequence within an inverse type II β‐turn as a new kind of pharmacophoric motif for μ‐opioid receptor (MOR) cyclopeptide agonists. Initially, we observed that c[Tyr‐D ‐Pro‐D ‐Trp‐Phe‐Gly] ( 4 ), an analogue of endomorphin‐1 (H‐Tyr‐Pro‐Trp‐Phe‐NH2) lacking the crucial protonatable amino group of Tyr 1, is a MOR agonist with 10?8 M affinity. Molecular docking analysis suggested that the relevant interactions with the receptor involve D ‐Trp‐Phe. The bioactive conformation of this region was investigated by selected derivatives of 4 designed to adopt an inverse type II β‐turn. These efforts led to c[Tyr‐Gly‐D ‐Trp‐Phe‐Gly] ( 14 ) and to the cyclotetrapeptide c[D ‐Asp‐1‐amide‐β‐Ala‐D ‐Trp‐Phe] ( 15 ), showing improved nanomolar affinity. Both 14 and 15 selectively bind MOR, as they have negligible affinity for the κ‐ and δ‐opioid receptors. Both 14 and 15 behave as partial MOR agonists in functional assays. Conformational and docking analyses confirm the role of the inverse β‐turn in binding. These results indicate that the D ‐Trp‐Phe inverse β‐turn structure can be used for designing non‐endomorphin‐like peptidomimetic opioid agonists in general, characterized by an atypical mechanism of interaction between ligand and receptor. 相似文献
34.
Cozza G Gianoncelli A Bonvini P Zorzi E Pasquale R Rosolen A Pinna LA Meggio F Zagotto G Moro S 《ChemMedChem》2011,6(12):2273-2286
Casein kinase 2 (CK2) is a ubiquitous, essential, and highly pleiotropic protein kinase; its abnormally high constitutive activity is suspected to underlie its pathogenic potential in neoplasia and other relevant diseases. Previously, using different in silico screening approaches, two potent and selective CK2 inhibitors were identified by our group: ellagic acid, a naturally occurring tannic acid derivative (K(i)=20 nM) and 3,8-dibromo-7-hydroxy-4-methylchromen-2-one (DBC, K(i)=60 nM). Comparing the crystallographic binding modes of both ellagic acid and DBC, an X-ray structure-driven merging approach was taken to design novel CK2 inhibitors with improved target affinity. A urolithin moiety is proposed as a possible bridging scaffold between the two known CK2 inhibitors, ellagic acid and DBC. Optimization of urolithin A as the bridging moiety led to the identification of 4-bromo-3,8-dihydroxy-benzo[c]chromen-6-one as a novel, potent and selective CK2 inhibitor, which shows a K(i) value of 7 nM against the protein kinase, representing a significant improvement in affinity for the target compared with the two parent fragments. 相似文献
35.
Righi V Di Nunzio M Danesi F Schenetti L Mucci A Boschetti E Biagi P Bonora S Tugnoli V Bordoni A 《Lipids》2011,46(7):627-636
It is well recognized that a high dietary intake of long-chain polyunsaturated fatty acids (LC-PUFA) has profound benefits
on health and prevention of chronic diseases. In particular, in recent years there has been a dramatic surge of interest in
the health effects of n-3 LC-PUFA derived from fish, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. Notwithstanding,
the metabolic fate and the effects of these fatty acids once inside the cell has seldom been comprehensively investigated.
Using cultured neonatal rat cardiomyocytes as model system we have investigated for the first time, by means of high-resolution
magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy in combination with gas chromatography (GC), the
modification occurring in the cell lipid environment after EPA and DHA supplementation. The most important difference between
control and n-3 LC-PUFA-supplemented cardiomyocytes highlighted by HR-MAS NMR spectroscopy is the increase of signals from
mobile lipids, identified as triacylglycerols (TAG). The observed increase of mobile TAG is a metabolic response to n-3 LC-PUFA
supplementation, which leads to an increased lipid storage. The sequestration of mobile lipids in lipid bodies provides a
deposit of stored energy that can be accessed in a regulated fashion according to metabolic need. Interestingly, while n-3
LC-PUFA supplementation to neonatal rat cardiomyocytes causes a huge variation in the cell lipid environment, it does not
induce detectable modifications in water-soluble metabolites, suggesting negligible interference with normal metabolic processes. 相似文献
36.
Chiara Agrati Alessandra Sacchi Eleonora Tartaglia Alessandra Vergori Roberta Gagliardini Alessandra Scarabello Michele Bibas 《International journal of molecular sciences》2021,22(15)
In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention. 相似文献
37.
38.
Daniela Ubiali Carla D. Serra Immacolata Serra Carlo F. Morelli Marco Terreni Alessandra M. Albertini Paolo Manitto Giovanna Speranza 《Advanced Synthesis \u0026amp; Catalysis》2012,354(1):96-104
Purine nucleoside phosphorylase (PNP) from Aeromonas hydrophila encoded by the deoD gene has been over‐expressed in Escherichia coli, purified, characterized about its substrate specificity and used for the preparative synthesis of some 6‐substituted purine‐9‐ribosides. Substrate specificity towards natural nucleosides showed that this PNP catalyzes the phosphorolysis of both 6‐oxo‐ and 6‐aminopurine (deoxy)ribonucleosides. A library of nucleoside analogues was synthesized and then submitted to enzymatic phosphorolysis as well. This assay revealed that 1‐, 2‐, 6‐ and 7‐modified nucleosides are accepted as substrates, whereas 8‐substituted nucleosides are not. A few transglycosylation reactions were carried out using 7‐methylguanosine iodide ( 4 ) as a D ‐ribose donor and 6‐substituted purines as acceptor. In particular, following this approach, 2‐amino‐6‐chloropurine‐9‐riboside ( 2c ), 6‐methoxypurine‐9‐riboside ( 2d ) and 2‐amino‐6‐(methylthio)purine‐9‐riboside ( 2g ) were synthesized in very high yield and purity. 相似文献
39.
Cristina Di Carluccio Enrique Crisman Prof. Yoshiyuki Manabe Rosa Ester Forgione Dr. Alessandra Lacetera Dr. Jussara Amato Dr. Bruno Pagano Prof. Antonio Randazzo Prof. Angela Zampella Prof. Rosa Lanzetta Prof. Koichi Fukase Prof. Antonio Molinaro Prof. Paul R. Crocker Prof. Sonsoles Martín-Santamaría Dr. Roberta Marchetti Prof. Alba Silipo 《Chembiochem : a European journal of chemical biology》2020,21(1-2):129-140
CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells. 相似文献
40.
Alessandra Dellaquila Gabriele Greco Elisabetta Campodoni Mauro Mazzocchi Barbara Mazzolai Anna Tampieri Nicola M. Pugno Monica Sandri 《应用聚合物科学杂志》2020,137(22):48739
Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano-coating that can act as biomimetic interface. Different bio-inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano-crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio-inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high-performance hybrid interfaces for bone tissue engineering. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48739. 相似文献