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排序方式: 共有261条查询结果,搜索用时 31 毫秒
1.
Dr. Simon Schramm Luca Agnetta Dr. Marcel Bermudez Hubert Gerwe Matthias Irmen Dr. Janine Holze Dr. Timo Littmann Prof. Gerhard Wolber Dr. Christian Tränkle Prof. Michael Decker 《ChemMedChem》2019,14(14):1349-1358
Recently, investigations of the complex mechanisms of allostery have led to a deeper understanding of G protein-coupled receptor (GPCR) activation and signaling processes. In this context, muscarinic acetylcholine receptors (mAChRs) are highly relevant due to their exemplary role in the study of allosteric modulation. In this work, we compare and discuss two sets of putatively dualsteric ligands, which were designed to connect carbachol to different types of allosteric ligands. We chose derivatives of TBPB [1-(1′-(2-tolyl)-1,4′-bipiperidin-4-yl)-1H-benzo[d]imidazol-2(3H)-one] as M1-selective putative bitopic ligands, and derivatives of benzyl quinolone carboxylic acid (BQCA) as an M1 positive allosteric modulator, varying the distance between the allosteric and orthosteric building blocks. Luciferase protein complementation assays demonstrated that linker length must be carefully chosen to yield either agonist or antagonist behavior. These findings may help to design biased signaling and/or different extents of efficacy. 相似文献
2.
Landsiedel Justus Root Waleri Schramm Christian Menzel Alexander Witzleben Steffen Bechtold Thomas Pham Tung 《Nano Research》2020,13(10):2658-2664
Nano Research - Development of colored surfaces by formation of nano-structured aggregates is a widely used strategy in nature to color lightweight structures (e.g. butterflies) without the use of... 相似文献
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Mobility and profiles of polychlorinated dibenzo-p-dioxins and dibenzofurans in sediment of Ya-Er Lake, China 总被引:1,自引:0,他引:1
The sediment of Ya-Er Lake had been heavily polluted by polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) from the former chloralkali industry. The total amounts of PCDD/Fs and I-TEQ decreased along the water flow direction and also decreased from top to bottom layers of sediment cores. Sediment of Pond 1 was dominated by PCDF. especially TCDF. In contrast, in the other four ponds, PCDD dominated in all layers and octachlorinated dibenzo-p-dioxin (OCDD) predominated in all of the homologues. When homologue profiles from sediments and water samples were compared using principal component analysis (PCA), the first two principal components represented 95.2% of the variance in the data. The first component explained 75.9% of the variance and the second one 19.3%. Two clusters were most distinct, presenting a shift in PCDD/Fs composition from PCDF to heptachlorinated dibenzo-p-dioxin (HpCDD) and OCDD in sediments and water from Pond I to Ponds 2-5. The pattern variation between Pond I and Ponds 2-5 in Ya-Er Lake was most likely due to the change of process in the chemical plant after the dams between the ponds were built. The results of the present study also showed that log Koc of PCDD/Fs calculated from data of sediment and water in the field were comparable with theoretical log Koc. The results also implied that the concentrations of PCDD/Fs in water and sediments could be predicted from each other by log Koc. 相似文献
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Untreated cotton fabrics and cotton samples pretreated with 1,2,3,4-butanetetracarboxylic acid were functionalised with an organotrialkoxysilane [(3-glycidyloxy)propyltrimethoxysilane] in conjunction with a metal alkoxide (aluminium isopropoxide, titanium tetraisopropoxide, or zircon tetrabutoxide). Evaluation of the physicomechanical properties revealed that the dry crease recovery angle was significantly increased in the case of aluminium isopropoxide, whereas the tensile strength and the tear strength were reduced. The application of alkyltrialkoxysilanes resulted in an enhanced contact angle. As the cotton samples were treated with hydrolysed metal alkoxides, which can function as mordants, the cotton fabrics were dyed with alizarin. The dyeing behaviour was determined from colorimetric data. 相似文献
6.
Schramm VL 《Accounts of chemical research》2003,36(8):588-596
The development of kinetic isotope effect methods for enzymatic reactions has resulted in the systematic determination of enzymatic transition state structure for several distinct chemical reaction mechanisms. Although it is early in the experimental development of the method, examples of concerted nucleophilic displacements (A(N)D(N) or S(N)2), aromatic nucleophilic displacements (A(N)D(N) or S(N)Ar), and both concerted and stepwise dissociative nucleophilic displacements (D(N)A(N) and D(N)A(N); S(N)1 reactions) have been exemplified. The transition state for each reaction exhibits a characteristic extent of bond-breaking and bond-making, defined here as transition state poise. Thus, concerted nucleophilic displacements (S(N)2 or D(N)A(N)) exhibit various extents of residual bond order to the leaving group and to the attacking nucleophile at the transition state. Aromatic nucleophilic displacements reach their rate-limiting transition states before or after formation of the tetrahedral intermediate. Several concerted, symmetric nucleophilic displacements at carbon have been described. Enzymatic transition state poise is summarized in a single diagram of bond orders using the terminology of Jencks. The analysis reveals enzymatic contributions to transition state poise, provides precedent for assignment of reaction types, and summarizes the current status of the experimental characterization of enzymatic transition states. Binding strengths of transition state analogues are readily correlated with transition state poise. 相似文献
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Heqing Shen Bernhard Henkelmann Walter Albert Rambeck Richard Mayer Ulrich Wehr Karl-Werner Schramm 《Food chemistry》2012
As one of the most important animal food sources, pigs are an important model in the assessment of human exposure to persistent organic pollutants (POPs). In the present study, the distribution of the administrated polychlorodibenzo-p-dioxin/furan (PCDD/F)–polychlorinated biphenyl (PCB) mixture and polybrominated diphenyl ethers (PBDEs) in the different tissues of pigs, including liver, lung, kidney, subcutaneous fat, mesentery and muscle, for understanding the physiologically based pollutant accumulation in these tissues and their edible safety was investigated. It was found that liver had a much higher potential to accumulate PCDD/Fs and dioxin-like pollutants like PCB-126 than the other tissues, but it did not specifically concentrate PBDE congeners as compared to the other tissues. The different PCDD/F congeners and PCB-126 followed a similar distribution pattern in the different tissues; also the different PBDE congeners have the similar pattern in these tissues. The liver’s higher concentrating potency for dioxin-like pollutants may result from its detoxification function, however, it can concentrate dioxin-like pollutants but not PBDEs may suggest that it is the toxicity but not lipophilic property of these POPs dominated their accumulation in liver tissues. Also the result suggested that liver is a high-risk edible tissue for dioxin-like pollutants. In conclusion, the present study suggested that physiologically based assessments are necessary for evaluating edible tissue safety in animal source foods. 相似文献
9.
Gunter Schramm 《The Annals of Regional Science》1987,21(3):60-79
This paper develops a strategy for the continuing and improved supply of woodfuels to urban and industrial consumers in Sub-Sahara Africa. It argues that continued use of these fuels is not only a necessity, but is also in the best economic interest of most of the countries in this region. It shows that intensified and more orderly utilization of woodfuels can help to enhance, rather than impinge upon environmental parameters. Some examples are provided that illustrate how such strategies can be put into practice. 相似文献
10.
In an earlier paper2 the authors have given the particle analysis and other tests of a number of English china clays, one English ball clay and several domestic kaolins. In this paper are presented the following additional data for the same clays: the carbon content as a measure of organic matter; the change in state of dispersion with pH for 20% slips as determined by settling tests; the change in viscosity with pH as determined with 40% slips; the alkali absorption for 20% and 40% slips. The more plastic clays are characterized by high organic content, high alkali absorption, and dispersion at low pH. Casting slips made up with the different china clays and two ball clays in varying proportions show that ball clay causes fluidity and that the plastic china clays produce more viscous slips than the less plastic. 相似文献