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811.
On the in vitro and in vivo properties of four locked nucleic acid nucleotides incorporated into an anti-H-Ras antisense oligonucleotide 总被引:1,自引:0,他引:1
Fluiter K Frieden M Vreijling J Rosenbohm C De Wissel MB Christensen SM Koch T Ørum H Baas F 《Chembiochem : a European journal of chemical biology》2005,6(6):1104-1109
Locked nucleic acid (beta-D-LNA) monomers are conformationally restricted nucleotides bearing a methylene 2'-O, 4'-C linkage that have an unprecedented high affinity for matching DNA or RNA. In this study, we compared the in vitro and in vivo properties of four different LNAs, beta-D-amino LNA (amino-LNA), beta-D-thio LNA (thio-LNA), beta-D-LNA (LNA), and its stereoisomer alpha-L-LNA in an antisense oligonucleotide (ODN). A well-known antisense ODN design against H-Ras was modified at the 5'- and 3'-ends with the different LNA analogues (LNA-DNA-LNA gapmer design). The resulting gapmers were tested in cancer-cell cultures and in a nude-mouse model bearing prostate tumor xenografts. The efficacy in target knockdown, the biodistribution, and the ability to inhibit tumor growth were measured. All anti H-Ras ODNs were very efficient in H-Ras mRNA knockdown in vitro, reaching maximum effect at concentrations below 5 nM. Moreover, the anti-H-Ras ODN containing alpha-L-LNA had clearly the highest efficacy in H-Ras knockdown. All LNA types displayed a great stability in serum. ODNs containing amino-LNA showed an increased uptake by heart, liver, and lungs as compared to the other LNA types. Both alpha-L-LNA and LNA gapmer ODNs had a high efficacy of tumor-growth inhibition and were nontoxic at the tested dosages. Remarkably, in vivo tumor-growth inhibition could be observed at dosages as low as 0.5 mg kg(-1) per day. These results indicate that alpha-L-LNA is a very promising member of the family of LNA analogues in antisense applications. 相似文献
812.
Jorge F. Toro-Vazquez Elena Dibildox-Alvarado Miriam Charó-Alonso Veronica Herrera-Coronado Carlos A. Gómez-Aldapa 《Journal of the American Oil Chemists' Society》2002,79(9):855-866
The behavior of the Avrami plot during TAG crystallization was studied by DSC and rheological measurements in oil blends of
palm stearin (26 and 80%) in sesame oil, using different crystallization temperatures (T
Cr
o) attained under several cooling rate conditions (1, 10, and 30°C/min). In the same way, the relationship between the growth
mechanisms of TAG, measured by the Avrami index (n), and the mass fractal dimension (D) of the crystal network was investigated. This last parameter was measured as TAG crystallized in the oil blend under isothermal
conditions. Results showed that TAG crystallization in a vegetable oil involves the process of TAG lamellar development, nucleation,
and crystal growth. Each event occurred at a different rate and extent as affected by cooling rate and T
Cr
o, and as a function of crystallization time under isothemal conditions at a given cooling rate. Within this framework, we
proposed that n calculated from the second region of the Avrami plot is a parameter mainly associated with crystal growth, whereas n from the first region is associated more with nucleation. On the other hand, changes in D values followed the different polymorphic states developed by TAG as a function of T
Cr
o. Additionally, it was shown that, independent of the concentration of palm stearin in the oil blend, at cooling rates of
1 and 10°C/min the increase in n from ∼3 to ∼4 produced a curvilinear increase in D from ∼1.75 to ∼3.0. The growth mechanism of the TAG crystals (i.e., n), also affected the magnitude of D. However different behavior was observed in the n-D relationship when n<2.7 and at 30°C/min. 相似文献
813.
814.
Andrés Ramírez Aguilera Luis Enrique Bergues Cabrales Héctor Manuel Camué Ciria Yudelmis Soler Pérez Fidel Gilart González Maraelys Morales González Lisset Ortíz Zamora Fabiola Suárez Palencia Miriam Fariñas Salas Nailet Real Bestard Gustavo Sierra González Idelisa Bergues Cabrales 《Mathematics and computers in simulation》2010
The knowledge of the electric current density distribution generated by an electrode array is very useful in electrotherapy for tumor treatment. We propose an innovative mathematical approach that takes into account planar solid tumor elliptic geometry, electrical differences between it and its surrounding healthy tissue, and positioning of the electrodes with respect to tumor-surrounding healthy tissue interface. We show the distributions of the electric current density in leading order and first correction terms in a heterogeneous planar medium formed by two regions (tumor and its surrounding healthy tissue) in function of these parameters. The results show that when electrodes are completely inserted in tumor and/or its conductivity is higher than that of its surrounding healthy tissue, the electric current density lines concentrate more in tumor and its tumor-surrounding healthy tissue interface. No significant differences are reported between the electric current density distributions in leading-order and first-order correction for each parameter investigated. However, norm of this physical magnitude reveals that these distributions are different when the ratio between radius of the electrodes and radius of the tumor is less than 0.8. We conclude that the analytical modeling presented in this study is of practical interest because it provides a convenient way to visualize the electric current density distributions generated by an electrode elliptic array in order to efficiently destroy the localized planar tumors with the minimum damage to organism, through an increase of the potential applied to the electrodes, the tumor conductivity with respect to its surrounding healthy tissue and insertion of all electrodes into tumor. 相似文献
815.
Lomnytska MI Becker S Hellman K Hellström AC Souchelnytskyi S Mints M Hellman U Andersson S Auer G 《Proteomics. Clinical applications》2010,4(1):17-31
Purpose: Cervical cancer is the second most prevalent malignancy of women. Our aim was to identify additional marker protein patterns for objective diagnosis of squamous cervical cancer (SCC). Experimental design: Collected tissue biopsies of SCC, squamous vaginal cancer (SVC), normal cervical and vaginal mucosa were subjected to 2‐DE, SameSpot analysis, MALDI‐TOF‐MS protein identification, and analysis of the expression of selected proteins by immunohistochemistry. Results: In 148 protein spots selected by the difference in expression 99 proteins were identified. A differential protein pattern for SCC was, e.g. over‐expressed (OE) eukaryotic translation initiation factor 3‐2β, neutrophil cytosolic factor 2, annexin A6 (ANXA6), for SVC it was OE cathepsin D, γ‐catenin, RAB2A, for both cancers it was OE apolipoprotein E, tropomyosin 3, HSPA8, and underexpressed cytokeratin 13, osteoglycin. In SCC nuclear expression of neutrophil cytosolic factor 2, PRDX2, HSP27 (nine of ten cases), ANXA6 (nine of ten cases) was observed while tropomyosin 4 was expressed only in two of ten cases. There was 81.1% (43/53) agreement between the expression of protein spots and the immune expression of proteins ( www.proteinatlas.org ). Conclusions and clinical relevance: SCC is characterized by specific tissue marker protein patterns that allow objective detection of the disease. They can become a basis for objective automated cytology‐based screening and improve current diagnostics of SCC. 相似文献
816.
Ehrensaft Miriam K.; Moffitt Terrie E.; Caspi Avshalom 《Canadian Metallurgical Quarterly》2004,113(2):258
In an unselected birth cohort (N=980, age 24-26 years), individuals in abusive relationships causing injury and/or official intervention (9% prevalence) were compared with participants reporting physical abuse without clinical consequences and with control participants who reported no abuse, on current characteristics and prospective developmental risks. In nonclinically abusive relationships, perpetrators were primarily women. In clinically abusive relationships, men and women used physical abuse, although more women needed medical treatment for injury. Women in clinically abusive relationships had childhood family adversity, adolescent conduct problems, and aggressive personality; men had disinhibitory psychopathology since childhood and extensive personality deviance. These findings counter the hibitory assumption that if clinical abuse was ascertained in epidemiological samples, it would be primarily man-to-woman, explained by patriarchy rather than psychopathology. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
817.
José J. Castro José R. Jiménez Carolina Ortiz Miriam Casares-López Sonia Ortiz-Peregrina 《Journal of Modern Optics》2017,64(13):1307-1314
The study of the visual function and optical quality of the eye has become a fundamental aim in the characterization of visual performance, especially in binocular vision, as this is our natural state of visual perception and because of its importance in clinical applications. Interocular asymmetry affects visual performance, and therefore its effect on different visual functions and stereopsis is of interest. In this work, we analyse interocular differences in optical quality (higher order aberrations and Strehl ratio) on the maximum disparity (the total range of stereoscopic perception) under mesopic conditions. We also analyse the relationship between the maximum disparity and the visual-discrimination capacity (halo perception) or binocular summation. The results in normal observers show a deterioration of the range of stereoscopic perception with the interocular differences in optical quality and with a higher perception of halos. Regarding the binocular summation for the visual functions studied, a positive correlation with the maximum disparity is found. 相似文献
818.
Iwona Bernacka‐Wojcik Miriam Huerta Klas Tybrandt Michal Karady Mohammad Yusuf Mulla David J. Poxson Erik O. Gabrielsson Karin Ljung Daniel T. Simon Magnus Berggren Eleni Stavrinidou 《Small (Weinheim an der Bergstrasse, Germany)》2019,15(43)
Electronic control of biological processes with bioelectronic devices holds promise for sophisticated regulation of physiology, for gaining fundamental understanding of biological systems, providing new therapeutic solutions, and digitally mediating adaptations of organisms to external factors. The organic electronic ion pump (OEIP) provides a unique means for electronically‐controlled, flow‐free delivery of ions, and biomolecules at cellular scale. Here, a miniaturized OEIP device based on glass capillary fibers (c‐OEIP) is implanted in a biological organism. The capillary form factor at the sub‐100 µm scale of the device enables it to be implanted in soft tissue, while its hyperbranched polyelectrolyte channel and addressing protocol allows efficient delivery of a large aromatic molecule. In the first example of an implantable bioelectronic device in plants, the c‐OEIP readily penetrates the leaf of an intact tobacco plant with no significant wound response (evaluated up to 24 h) and effectively delivers the hormone abscisic acid (ABA) into the leaf apoplast. OEIP‐mediated delivery of ABA, the phytohormone that regulates plant's tolerance to stress, induces closure of stomata, the microscopic pores in leaf's epidermis that play a vital role in photosynthesis and transpiration. Efficient and localized ABA delivery reveals previously unreported kinetics of ABA‐induced signal propagation. 相似文献
819.
Carolina Fonseca Couto Wagner Guadagnin Moravia Miriam Cristina Santos Amaral 《Clean Technologies and Environmental Policy》2017,19(8):2057-2073
This study investigates the application of a hybrid microfiltration–nanofiltration (MF–NF) process for textile wastewater reclamation. Indigo blue dye was efficiently retained by an MF membrane, allowing its recovery from the concentrated stream. NF technology was successfully applied to polish textile effluent. The NF membrane was evaluated under different transmembrane pressure (8–15 bars), crossflow velocities (0.21–0.84 cm s?1), pH (7–11), and feed temperature (20–40 °C). The best NF performance was provided at a pressure of 12 bar and a crossflow rate of 0.63 cm s?1. The NF performance (in terms of COD, conductivity, colour, and nitrogen removal) was not influenced by pH; however, higher feed pH values resulted in increased membrane fouling. The principal cause of flux decline was due to concentration polarization. Membrane chemical cleaning was sufficient to regain the initial permeability. The NF permeate met the quality requirements for all water demands within the textile industry, while the NF concentrate could be used to wash equipment, print work screens, print paste containers, and floors. The total capital cost (CapEx) of the MF–NF system was estimated at 58,362.50 US dollars and the total operational cost (OpEx) at 0.31 US dollars per cubic metre of effluent. 相似文献
820.
Bar Israeli Daniela S. Strugach Sigal Gelkop Shir Weber Dor S. Gozlan Miriam Amiram 《Advanced functional materials》2021,31(44):2011276
A general and versatile technology to engineer light-responsive protein-based biomaterials can enable the manipulation and interrogation of proteins, pathways, and cells, and it will assist the design of “smart” light-responsive biomaterials. This study reports the evolution of chromosomal aminoacyl-tRNA synthetases (aaRSs) for azobenzene-bearing unnatural amino acids (uAAs) with up to ≈40-fold increased protein production and improved fidelity, as compared with a previously described aaRS. The evolved translation systems enable efficient and accurate incorporation of up to 10 instances of the various light-responsive uAAs in elastin-like polypeptides (ELPs). Azobenzene-containing ELPs are capable of isothermal, reversible, light-mediated soluble-to-insoluble phase transition, with up to a 12 °C difference in the ELP transition temperature upon cis-to-trans azobenzene isomerization. Furthermore, the incorporation of azobenzene-uAAs in ELP diblock-copolymers enables the creation of light-responsive self-assembled nanostructures. Finally, light-responsive resilin-inspired polymers are also generated by multi-site azobenzene-incorporation. The translation machinery evolved in this study can be used for the multi-site incorporation of azobenzene moieties at the polypeptide level and constitute a universal methodology for the design of light-responsive proteins and additional families of protein-based biomaterials with customized and tunable light-responsive behavior. 相似文献