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101.
This research investigates the long‐term shrinkage and Relative Mass Loss (RML) of mature Portland concretes (pure CEMI and blended CEMV/A), at temperatures of 20°C and 80°C. When placed at 80°C and at relative humidities (RH) below 50‐60%, concrete shrinkage increases with very slow stabilization kinetics by several hundreds of μm/m, while RML remains of about 0.2%. The origins of this continued shrinkage, simultaneously with limited RML, are investigated through the changes in (i) the pore structure of the concretes (by Mercury Intrusion Porosimetry and nitrogen adsorption) and in (ii) their solid phases (by TGA/DTA, FTIR spectroscopy coupled to DVS, quantitative X‐Ray Diffraction by Rietveld analysis, and 29Si and 27Al MAS NMR). While the pore structure coarsens during continued shrinkage, several phase transformations occur, namely ettringite decomposition and changes in the silicate chain length of the C–A–S–H. While these structural changes are documented, their relationship with shrinkage/RML and to the pore structure is novel.  相似文献   
102.
We have previously shown that in HeLa cells treated with a variety of agents there is an increase in cell surface peptidase (CSP) activity in those cells undergoing apoptosis. The increase in CSP activity observed in UVB-irradiated cells undergoing apoptosis was unaffected when the cultures were treated with the aminopeptidase inhibitor bestatin, and matrix metalloprotease inhibitor BB3103, but greatly enhanced when treated with the caspase 3 inhibitor-DEVD, and reduced in the presence of the poly(ADP-ribose) polymerase (PARP) inhibitor-3-aminobenzamide (3AB). Neither 3AB nor DEVD had an effect on the gross morphology of the apoptotic cells observed under electron microscopy, nor did they have an effect on phosphatidylserine eversion on the cell membrane, or that of PARP cleavage. All the agents except for DEVD had no effect on the level of caspase 3 activity in the cells. The results suggest that other caspases may cleave PARP in these cells. Both 3AB and DEVD treatment reduced the level of actin cleavage seen in the apoptotic cells. The increase in CSP activity observed in cells undergoing UVB-induced apoptosis appears to involve PARP but not caspase 3.  相似文献   
103.
Graphene oxide hydrogels have been prepared by ultrasonication of precursor aqueous dispersions. The ultrasonication fractures the nanosheets, reducing their dimensions and exposing new sheet edges that do not possess the stabilizing carboxyl functional groups found along the edge of the as-prepared material. Ultrasonication does not affect the overall chemical functionality of the graphene oxide nanosheets, as spectra (carbon-13 nuclear magnetic resonance spectroscopy, infrared spectroscopy, and X-ray photoelectron spectroscopy) of samples before and after ultrasonication are nearly identical. Gelation is induced after only 30 min of ultrasonication to achieve a relatively weak gel with a shear modulus of 0.3 kPa; however, extension of ultrasonic treatment to 120 min yields a more robust hydrogel with a shear modulus of 1.6 kPa. Such enhancement in the gel’s physical properties can be attributed to the lack of stabilizing carboxyl groups on newly generated nanosheet fragments from the interior regions of the original nanosheets. As prepared, these hydrogels exhibit exceptionally low critical gelation concentrations ranging from ~0.050 to ~0.125 mg mL?1 that can be tuned according to the extent of ultrasonic treatment.  相似文献   
104.
Compounds that simultaneously activate peroxisome proliferator‐activated receptor (PPAR) subtypes α and γ have the potential to effectively treat dyslipidemia and type 2 diabetes (T2D) in a single pharmaceutically active molecule. The frequently observed side effects of selective PPARγ agonists, such as edema and weight gain, were expected to be overcome by using additive PPARα activity, leading to dual PPARα/γ agonists with balanced activity for both subtypes. Herein we report the discovery, synthesis, and optimization of a new series of α‐ethoxyphenylpropionic acid bearing 5‐ or 6‐substituted indoles. The incorporation of oxime ethers on the carbonyl portion of the benzoyl group can bring the PPARα/γ potency ratio equal to or slightly greater than one, as is the case for compounds 20 c and 21 a . Compound 20 c shows high efficacy in an ob/ob mouse model of T2D and dyslipidemia, similar to that of rosiglitazone and tesaglitazar, but with a significant increase in body weight gain. In contrast, compound 21 a , less potent as a dual PPARα/γ activator than 20 c , showed an interesting pharmacological profile, as it elicits a decrease in body weight relative to reference compounds.  相似文献   
105.
The ever‐growing number of pathogenic bacteria resistant to treatment with antibiotics call for the development of novel compounds with as‐yet unexplored modes of action. Here, we demonstrate the in vivo antibacterial activity of carba‐α‐d ‐glucosamine (CGlcN). In this mode of action study, we provide evidence that CGlcN‐mediated growth inhibition is due to glmS ribozyme activation, and we demonstrate that CGlcN hijacks an endogenous activation pathway, hence utilizing a prodrug mechanism. This is the first report describing antibacterial activity mediated by activating the self‐cleaving properties of a ribozyme. Our results open the path towards a compound class with an entirely novel and distinct molecular mechanism.  相似文献   
106.
107.
Crop-fallow systems dominate many semi-arid agricultural regions despite fallow’s negative effects on soil and water quality. Annual legumes grown as a fallow-replacement crop, and terminated prior to maturity, can reduce these negative effects without substantially decreasing plant available water for the subsequent crop. Interest in growing legume green manures (LGMs) in synthetically-fertilized systems is increasing in the northern Great Plains of North America, partly due to the N-fixing capabilities of legumes; however, little is known about the effects of planting and termination time on N fixation amounts in the region. A 2-year field study was initiated in southwest Montana to determine the effects of planting time (spring or summer) and termination time (e.g. flower or pod) on the amount of N fixed by field pea (Pisum sativum cv. Arvika) and lentil (Lens culinaris cv. Richlea). Two methods, 15N natural abundance and N difference, were used to quantify N fixation, with wheat or in-crop weeds as reference plants. In 2009, N fixed by spring-planted lentil was higher by pod than flower (P = 0.03). Termination time did not affect the amount of N fixed by spring-planted pea, despite more biomass by pod than flower. In 2010, both spring-planted crops fixed more N by pod than flower (P < 0.01) and more N was fixed by spring-planted than summer-planted crops (P < 0.01). These results should prove useful to growers interested in selecting management practices that optimize N fixation of LGMs.  相似文献   
108.
The aim of this study was to investigate soy protein recovery feasibility after lab- and pilot-plant scale oleosome isolation. The proteins were isolated by isoelectric precipitation and by ultrafiltration. The functional properties of the recovered proteins were compared to soy protein isolate produced in our laboratory. The residual lipid content in the aqueous supernatant affected the protein recovery yields and purities. Ethanol precipitation and ultrafiltration resulted in the best protein yields, which were 25 and 26% greater than protein yield obtained by isoelectric precipitation with distilled water dilution. The protein content of the isoelectric precipitated pilot-plant supernatant was higher (98%) than the protein content of ethanol-precipitated proteins (80%). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed similar peptide profiles for laboratory and pilot-plant supernatants. Protein solubility curves between pH 3 and 8 were typical for soy protein isolate with higher solubilities for proteins obtained from pilot-plant supernatant. The soy protein isolate and ethanol-precipitated protein had the highest emulsification capacity on a dry-weight basis. These desirable functional properties of proteins recovered as co-products after oleosome isolation suggest they are highly suitable for industrial application as food ingredients and their recovery would contribute to the economics of the overall oleosome fractionation process.  相似文献   
109.
The orexin system plays an important role in the regulation of wakefulness. Suvorexant, a dual orexin receptor antagonist (DORA) is approved for the treatment of primary insomnia. Herein, we outline our optimization efforts toward a novel DORA. We started our investigation with rac-[3-(5-chloro-benzooxazol-2-ylamino)piperidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-ylphenyl)methanone ( 3 ), a structural hybrid of suvorexant and a piperidine-containing DORA. During the optimization, we resolved liabilities such as chemical instability, CYP3A4 inhibition, and low brain penetration potential. Furthermore, structural modification of the piperidine scaffold was essential to improve potency at the orexin 2 receptor. This work led to the identification of (5-methoxy-4-methyl-2-[1,2,3]triazol-2-ylphenyl)-{(S)-2-[5-(2-trifluoromethoxyphenyl)-[1,2,4]oxadiazol-3-yl]pyrrolidin-1-yl}methanone ( 51 ), a potent, brain-penetrating DORA with in vivo efficacy similar to that of suvorexant in rats.  相似文献   
110.
The objective of the present work is to show the influence of machining and anodizing processes on fatigue life of alloy 7010-T7451. Two different cutting conditions were employed to obtain two different initial surface roughnesses. Degreasing, pickling and anodizing were then carried out. In the as machined condition, surface roughness is clearly effective in reducing fatigue life in this material. As the surface roughness increases fatigue life decreases and this effect is found to be more pronounced in high cycle fatigue where major portion of fatigue life is consumed in nucleating the cracks. Effects of pre-treatments, like degreasing and pickling employed prior to anodizing, on fatigue life of the given alloy were also studied. Fatigue curves showed that pickling had negative impact on fatigue life of specimens while degreasing showed no change in fatigue life. The small decrease in fatigue life of anodized specimens as compare to pickled specimens is attributed to brittle nature and micro-cracking of the coating. Scanning electron microscopic (SEM) examination revealed multi-site crack initiation for the pickled and anodized specimens. SEM examination also showed that pickling process attacked the grain boundaries and the inclusions present on the surface resulting in pits formation. These pits are of primary concern with respect to accelerated fatigue crack nucleation and subsequent anodized coating formation.  相似文献   
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