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排序方式: 共有297条查询结果,搜索用时 359 毫秒
51.
Lucie Pigeon Cristine Gonçalves David Gosset Chantal Pichon Patrick Midoux 《Small (Weinheim an der Bergstrasse, Germany)》2013,9(22):3845-3851
Chemical vectors as cationic polymers and cationic lipids are promising alternatives to viral vectors for gene therapy. Beside endosome escape and nuclear import, plasmid DNA (pDNA) migration in the cytosol toward the nuclear envelope is also regarded as a limiting step for efficient DNA transfection with non‐viral vectors. Here, the interaction between E3‐14.7K and FIP‐1 to favor migration of pDNA along microtubules is exploited. E3‐14.7K is an early protein of human adenoviruses that interacts via FIP‐1 (Fourteen.7K Interacting Protein 1) protein with the light‐chain components of the human microtubule motor protein dynein (TCTEL1). This peptide is conjugated with pDNA and mediates interaction of pDNA in vitro with isolated microtubules as well as with microtubules in cellulo. Videomicroscopy and tracking treatment of images clearly demonstrate that P79‐98/pDNA conjugate exhibits a linear transport with large amplitude along microtubules upon 2 h transfection with polyplexes whereas control pDNA conjugate exhibits small non‐directional movements in the cytoplasm. Remarkably, P79‐98/peGFP polyplexes enhance by a factor 2.5 (up to 76%) the number of transfected cells. The results demonstrate, for the first time, that the transfection efficiency of polyplexes can be drastically increased when the microtubules migration of pDNA is facilitated by a peptide allowing pDNA docking to TCTEL1. This is a real breakthrough in the non viral gene delivery field that opens hope to build artificial viruses. 相似文献
52.
Lamboy JA Tam PY Lee LS Jackson PJ Avrantinis SK Lee HJ Corn RM Weiss GA 《Chembiochem : a European journal of chemical biology》2008,9(17):2846-2852
An Achilles heel inherent to all molecular display formats, background binding between target and display system introduces false positives into screens and selections. For example, the negatively charged surfaces of phage, mRNA, and ribosome display systems bind with unacceptably high nonspecificity to positively charged target molecules, which represent an estimated 35% of proteins in the human proteome. Here we report the first systematic attempt to understand why a broad class of molecular display selections fail, and then solve the underlying problem for both phage and RNA display. Firstly, a genetic strategy was used to introduce a short, charge-neutralizing peptide into the solvent-exposed, negatively charged phage coat. The modified phage (KO7(+)) reduced or eliminated nonspecific binding to the problematic high-pI proteins. In the second, chemical approach, nonspecific interactions were blocked by oligolysine wrappers in the cases of phage and total RNA. For phage display applications, the peptides Lys(n) (where n=16 to 24) emerged as optimal for wrapping the phage. Lys(8), however, provided effective wrappers for RNA binding in assays against the RNA binding protein HIV-1 Vif. The oligolysine peptides blocked nonspecific binding to allow successful selections, screens, and assays with five previously unworkable protein targets. 相似文献
53.
Cerovský V Hovorka O Cvacka J Voburka Z Bednárová L Borovicková L Slaninová J Fucík V 《Chembiochem : a European journal of chemical biology》2008,9(17):2815-2821
A novel antimicrobial peptide designated melectin was isolated from the venom of the cleptoparasitic bee Melecta albifrons. Its primary sequence was established as H-Gly-Phe-Leu-Ser-Ile-Leu-Lys-Lys-Val-Leu-Pro-Lys-Val-Met-Ala-His-Met-Lys-NH(2) by Edman degradation and ESI-QTOF mass spectrometry. Synthetic melectin exhibited antimicrobial activity against both gram-positive and -negative bacteria and it degranulated rat peritoneal mast cells, but its hemolytic activity was low. The CD spectra of melectin measured in the presence of trifluoroethanol and sodium dodecyl sulfate showed a high content alpha-helices, which indicates that melectin can adopt an amphipathic alpha-helical secondary structure in an anisotropic environment such as the bacterial cell membrane. To envisage the role of the proline residue located in the middle of the peptide chain on biological activity and secondary structure, we prepared several melectin analogues in which the Pro11 residue was either replaced by other amino acid residues or was omitted. The results of biological testing suggest that a Pro kink in the alpha-helical structure of melectin plays an important role in selectivity for bacterial cells. In addition, a series of N- and C-terminal-shortened analogues was synthesized to examine which region of the peptide is related to antimicrobial activity. 相似文献
54.
In many developing urban settings, economic growth and motorization are coupled with increasing rates of road traffic injuries (RTIs). By highlighting typical sites and circumstances at/in which car crashes occur, more specific targets for prevention can be identified. The study is based on police data for a 1-year period and covers the Chaoyang District, the biggest district of Beijing City. Focus is placed on crash patterns and their distribution by types of road and areas. Both fatal and non-fatal crashes are considered (n=754). In the main, the crashes occurred in relatively favorable driving circumstances (e.g., sunny weather, flat and straight roads, asphalted roads, and good traffic signals and road markings). They were also quite evenly distributed over time of day, day of week and season. Five crash patterns were highlighted, of which three were strongly associated with specific areas and four with specific types of road. The study supports the idea that type of road and RTI severity or pattern are closely related. It contributes to the development of context-relevant prevention measures aimed at reducing road crashes and minimizing their consequences and also supports safe planning of the road traffic environment. 相似文献
55.
56.
Radka Podlipn Martina Navrtilov Lucie Raisov Stuchlíkov Kateina Mokov Lenka Langhansov Lenka Sklov Barbora Szotkov 《International journal of molecular sciences》2021,22(13)
Although manure is an important source of minerals and organic compounds it represents a certain risk of spreading the veterinary drugs in the farmland and their permeation to human food. We tested the uptake of the anthelmintic drug fenbendazole (FBZ) by soybean, a common crop plant, from the soil and its biotransformation and accumulation in different soybean organs, including beans. Soybeans were cultivated in vitro or grown in a greenhouse in pots. FBZ was extensively metabolized in roots of in vitro seedlings, where sixteen metabolites were identified, and less in leaves, where only two metabolites were found. The soybeans in greenhouse absorbed FBZ by roots and translocated it to the leaves, pods, and beans. In roots, leaves, and pods two metabolites were identified. In beans, FBZ and one metabolite was found. FBZ exposure did not affect the plant fitness or yield, but reduced activities of some antioxidant enzymes and isoflavonoids content in the beans. In conclusion, manure or biosolids containing FBZ and its metabolites represent a significant risk of these pharmaceuticals entering food consumed by humans or animal feed. In addition, the presence of these drugs in plants can affect plant metabolism, including the production of isoflavonoids. 相似文献
57.
Identification of molecular species of various N-acylated bacteriohopanehexol-mannosamides from the thermophilic bacterium Alicyclobacillus acidoterrestris by semipreparative HPLC and by RP-HPLC with ESI is described. We used triple-quadrupole type mass spectrometer, 1H and 13C NMR for analyzing this complex lipid. CD spectra of two compounds (model compound—7-deoxy-d-glycero-d-allo-heptitol obtained by stereospecific synthesis, and an isolated derivative of hopane) were also measured and the absolute
configuration of both compounds was determined. On the basis of all the above methods, we identified the full structure of
a new class of bacteriohopanes, represented by various N-acylated bacteriohopanehexol-mannosamides. 相似文献
58.
Ayi Fanou L Mobio TA Creppy EE Fayomi B Fustoni S Møller P Kyrtopoulos S Georgiades P Loft S Sanni A Skov H Ovrebø S Autrup H 《The Science of the total environment》2006,358(1-3):85-96
Exposure to genotoxic compounds present in ambient air has been studied in Cotonou, Benin, a city where two-stroke motorbikes are the major form of transportation and gasoline quality is poor. Personal monitoring and biomarkers were used to assess the exposure. Non-smoking taxi-moto drivers (city) and village residents were the study subjects. Benzene exposure was significantly higher in the city, as compared to the village (76.0+/-26.8 microg/m(3) versus 3.4+/-3.0, p=0.0004). Urinary excretion of benzene and S-phenylmercapturic acid (S-PMA) were also highest in subjects living in the city, whereas 1-hydroxypyrene was not different. The level of total polycyclic aromatic hydrocarbons (PAHs), associated with particles, ranged from 76.21 to 103.23 in Cotonou versus 1.55 ng/m(3) for the village. Determination of DNA damage in lymphocytes showed that subjects from the city had elevated number of lesions compared to subjects in the village in terms of bulky DNA adducts, 8-hydroxy-2'-deoxyguanosine and 5-methylcytosine, whereas DNA fragmentations analysed by alkaline gel electrophoresis was not different between the subjects. In conclusion, this study shows that air pollution is pronounced in Cotonou, Bénin and is associated with elevated levels of DNA damage in residents of the city compared to people living in a non-polluted rural village. 相似文献
59.
Monika Absolonová Lucie Melounková Dr. Jaromír Vinklárek Dr. Jan Honzíček Libor Dostál Dr. Ondřej Mrózek 《ChemMedChem》2021,16(11):1805-1813
Cytotoxic complexes containing molybdenum are widely studied as a potential substitution for commercially used drugs that often suffer from pronounced side effects and cellular resistance. Compounds of the type [(η5-Cp′)Mo(CO)2(N,NL)][BF4], where Cp is cyclopentadienyl and N,NL is a bidentate ligand, are well known for their strong anticancer activity. It is a generally accepted paradigm that the nature of the coordinated N,NL ligand has a major impact on the cytotoxicity. In this study, a series of new functionalised Cp complexes of molybdenum was synthesised from derivatised fulvenes as π-ligand precursors. Indeed, the coordination sphere‘s modulation by various N,N-chelating ligands afforded species active toward leukemic cell line MOLT-4 with IC50 values depending on the character of the N,N-chelator used. However, following study clearly showed that functionalisation of the Cp ring with an amine moiety considerably improved cytotoxicity. These results are of crucial importance for the future design of highly active cytotoxic drugs, as modification of cyclopentadienyl is believed to have a minor effect on biological activity. 相似文献
60.
Dr. Angelo Frei Soumya Ramu Gabrielle J. Lowe Dr. Hue Dinh Dr. Lucie Semenec Dr. Alysha G. Elliott Johannes Zuegg Dr. Anke Deckers Prof. Nicole Jung Prof. Stefan Bräse Dr. Amy K. Cain Prof. Mark A. T. Blaskovich 《ChemMedChem》2021,16(20):3165-3171
Antimicrobial resistance is a looming health crisis, and it is becoming increasingly clear that organic chemistry alone is not sufficient to continue to provide the world with novel and effective antibiotics. Recently there has been an increased number of reports describing promising antimicrobial properties of metal-containing compounds. Platinum complexes are well known in the field of inorganic medicinal chemistry for their tremendous success as anticancer agents. Here we report on the promising antibacterial properties of platinum cyclooctadiene (COD) complexes. Amongst the 15 compounds studied, the simplest compounds Pt(COD)X2 (X=Cl, I, Pt1 and Pt2 ) showed excellent activity against a panel of Gram-positive bacteria including vancomycin and methicillin resistant Staphylococcus aureus. Additionally, the lead compounds show no toxicity against mammalian cells or haemolytic properties at the highest tested concentrations, indicating that the observed activity is specific against bacteria. Finally, these compounds showed no toxicity against Galleria mellonella at the highest measured concentrations. However, preliminary efficacy studies in the same animal model found no decrease in bacterial load upon treatment with Pt1 and Pt2 . Serum exchange studies suggest that these compounds exhibit high serum binding which reduces their bioavailability in vivo, mandating alternative administration routes such as e. g. topical application. 相似文献