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91.
pH‐Cleavable Nucleoside Lipids: A New Paradigm for Controlling the Stability of Lipid‐Based Delivery Systems 下载免费PDF全文
Dr. Khalid Oumzil Sébastien Benizri Giovanni Tonelli Dr. Cathy Staedel Ananda Appavoo Max Chaffanet Laurence Navailles Prof. Philippe Barthélémy 《ChemMedChem》2015,10(11):1797-1801
Lipid‐based delivery systems are an established technology with considerable clinical acceptance and several applications in human. Herein, we report the design, synthesis and evaluation of novel orthoester nucleoside lipids (ONLs) for the modulation of liposome stability. The ONLs contain head groups with 3′‐orthoester nucleoside derivatives featuring positive or negative charges. The insertion of the orthoester function in the NL structures allows the formation of pH‐sensitive liposomes. ONL‐based liposomes can be hydrolyzed to provide nontoxic products, including nucleoside derivatives and hexadecanol. To allow the release to be tunable at different hydrolysis rates, the charge of the polar head structure is modulated, and the head group can be released at a biologically relevant pH. Crucially, when ONLs are mixed with natural phosphocholine lipids (PC), the resultant liposome evolves toward the formation of a hexadecanol/PC lamellar system. Biological evaluation shows that stable nucleic acid lipid particles (SNALPs) formulated with ONLs and siRNAs can effectively enter into tumor cells and release their nucleic acid payload in response to an intracellular acidic environment. This results in a much higher antitumor activity than conventional SNALPs. The ability to use pH‐cleavable nucleolipids to control the stability of lipid‐based delivery systems represents a promising approach for the intracellular delivery of drug cargos. 相似文献
92.
Jethro Akroyd Alastair J. Smith Laurence R. McGlashan Markus Kraft 《Chemical engineering science》2010,65(6):1915-1924
This paper investigates a mean reaction rate closure for turbulent reacting flows called the Direct Quadrature Method of Moments using the Interaction by Exchange with the Mean micromixing model (DQMoM-IEM). The method was first introduced for reacting flows by Fox (Computational Models for Turbulent Reacting Flows, Cambridge University Press, 2003). We present a systematic study that considers several important new aspects of the method. In particular we introduce a new analytic expression for the DQMoM-IEM source terms. We present a rigourous numerical investigation and discuss problems of boundedness and singularity in detail. We introduce a filter function to overcome these issues in the general case and present analytic integrals for special cases of specific terms. We extend the methodology to take advantage of these developments and show details of the implementation in a commercial computational fluid dynamics (CFD) code. We present an extensive set of numerical experiments and validation. The method is proven for a problem known from the literature which includes an isothermal dimerisation process. Experimental and transported probability density function (PDF) data compare reasonably well. The method is discussed critically and areas for further research are suggested to make the method more practical. 相似文献
93.
Emma L. Bradley Laurence Castle Andrew P. Damant Sue M. Jickells Mark R. Philo 《Journal of Coatings Technology and Research》2010,7(4):477-483
Glass–fiber-reinforced plastic (GRP) vats are used widely for the storage of foodstuffs and potable water. As the inner surfaces
deteriorate during decades of use, they need to be repaired. The unsaturated polyester resins that are used for recoating
are crosslinked with styrene which can cause taint and odor problems. This article describes some coating parameters that
affect the content of residual styrene and its subsequent migration. The influences of cure temperature and duration, along
with the effect of washing with warm detergent solution, were investigated. Cured specimens were tested for their residual
styrene content and for styrene migration into the food simulants, distilled water, 3% acetic acid, and 15% ethanol. The dominant
factor in reducing the amount of residual styrene is the temperature. The resin self-heats as it cures, typically up to 50°C.
Thus, any further lowering of the styrene content requires a higher cure temperature than this. A 3-h cure at 80°C reduced
both the residual content and the migration levels by about 100-fold. At lower cure temperatures, the heating effect of washing
at 60°C is more important than the washing effect of the detergent. When less catalyst was used the residual styrene levels
rose dramatically, from 70 to 360 to 1300 mg/kg for the normal dose, half and quarter the normal dose, respectively. There
was a linear relationship between residual content in the GRP and the migration levels. This correlation could be used for
monitoring the quality of vats repaired in situ, using styrene-based coating resins. 相似文献
94.
Meybeck M Lestel L Bonté P Moilleron R Colin JL Rousselot O Hervé D de Pontevès C Grosbois C Thévenot DR 《The Science of the total environment》2007,375(1-3):204-231
The Driver-Pressures-State-Impact-Response approach is applied to heavy metals in the Seine River catchment (65,000 km(2); 14 million people of which 10 million are aggregated within Paris megacity; 30% of French industrial and agricultural production). The contamination pattern at river mouth is established on the particulate material at different time scales: 1930-2000 for floodplain cores, 1980-2003 for suspended particulate matter (SPM) and bed-sediments, 1994-2003 for atmospheric fallout and annual flood deposits. The Seine has been among the most contaminated catchments with maximum contents recorded at 130 mg kg(-1) for Cd, 24 for Hg, 558 for Pb, 1620 for Zn, 347 for Cu, 275 for Cr and 150 for Ni. Today, the average levels for Cd (1.8 mg kg(-1)), Hg (1.08), Pb (108), Zn (370), Cu (99), Cr (123) and Ni (31) are much lower but still in the upper 90% of the global scale distribution (Cr and Ni excepted) and well above the natural background values determined on pre-historical deposits. All metal contents have decreased at least since 1955/65, well before metal emission regulations that started in the mid 1970's and the metal monitoring in the catchment that started in the early 1980's. In the last 20 y, major criteria changes for the management of contaminated particulates (treated urban sludge, agricultural soils, dredged sediments) have occurred. In the mid 1990's, there was a complete shift in the contamination assessment scales, from sediment management and water usage criteria to the good ecological state, now required by the 2000 European Directive. When comparing excess metal outputs, associated to river SPM, to the average metal demand within the catchment from 1950 to 2000, the leakage ratios decrease exponentially from 1950 to 2000 for Cd, Cr, Cu, Pb and Zn, meanwhile, a general increase of the demand is observed: the rate of recycling and/or treatment of metals within the anthroposphere has been improved ten-fold. Hg environmental trajectory is very specific: there is a marked decontamination from 1970 to 2000, but the leakage ratio remains very high (10 to 20%) during this period. Drivers and Pressures are poorly known prior to 1985; State evolution since 1935 has been reconstructed from flood plain cores analysis; Impacts were maximum between 1950 and 1970 but remained unknown due to analytical limitation and lack of awareness. Some Responses are lagging 10 y behind monitoring and have much evolved in the past 10 y. 相似文献
95.
96.
Maria C. F. Ferreira Delia Kesner Laurence Puel 《Applicable Algebra in Engineering, Communication and Computing》1999,9(4):333-371
This paper studies preservation of β-strong normalization by two different confluent λ-calculi with explicit substitutions
defined in [96]; the particularity of these calculi, called λ
d
and λ
dn
respectively, is that both have a (weak) composition operator for substitutions. We apply an abstract simulation technique
to reduce preservation of β-strong normalization of λ
d
and λ
dn
to that of another calculus, called λ
f
having no composition operator. Then, preservation of β-strong normalization of λ
f
is shown using the same technique as in [2]. As a consequence, λ
d
and λ
dn
become the first λ-calculi with explicit substitutions having (weak) composition and preserving β-strong normalization. As
an aside, we also show how to apply our technique to reduce preservation of β-strong normalization of the calculus λ
v
in [20] to that of λ
f
.
Received: August 19, 1997; revised version: November 13, 1998 相似文献
98.
Takagi S Frukhtbeyn S Chow LC Sugawara A Fujikawa K Ogata H Hayashi M Ogiso B 《Journal of research of the National Institute of Standards and Technology》2010,115(4):267-276
This study reports for the first time in vitro and in vivo properties of fluorapatite (FA)-forming calcium phosphate cements (CPCs). The experimental cements contained from (0 to 3.1) mass % of F, corresponding to presence of FA at levels of approximately (0 to 87) mass %. The crystallinity of the apatitic cement product increased greatly with the FA content. When implanted subcutaneously in rats, the in vivo resorption rate decreased significantly with increasing FA content. The cement with the highest FA content was not resorbed in soft tissue, making it the first known biocompatible and bioinert CPC. These bioinert CPCs might be useful for applications where slow or no resorption of the implant is required to achieve the desired clinical outcome. 相似文献
99.
100.