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101.
Reddy GS Robinson M Wang G Palmore GT Gennaro L Vouros P De Clercq P Vandewalle M Young W Ling S Verstuyf A Bouillon R 《Archives of biochemistry and biophysics》2007,460(2):254-261
It is now well established that 1alpha,25(OH)2D3 is metabolized in its target tissues through the modifications of both side chain and A-ring. The C-24 oxidation pathway is the side chain modification pathway through which 1alpha,25(OH)2D3 is metabolized into calcitroic acid. The C-3 epimerization pathway is the A-ring modification pathway through which 1alpha,25(OH)2D3 is metabolized into 1alpha,25(OH)2-3-epi-D3. During the past two decades, a great number of vitamin D analogs were synthesized by altering the structure of both side chain and A-ring of 1alpha,25(OH)2D3 with the aim to generate novel vitamin D compounds that inhibit proliferation and induce differentiation of various types of normal and cancer cells without causing significant hypercalcemia. Previously, we used some of these analogs as molecular probes to examine how changes in 1alpha,25(OH)2D3 structure would affect its target tissue metabolism. Recently, several nonsteroidal analogs of 1alpha,25(OH)2D3 with unique biological activity profiles were synthesized. Two of the analogs, SL 117 and WU 515 lack the C-ring of the CD-ring skeleton of 1alpha,25(OH)2D3. SL 117 contains the same side chain as that of 1alpha,25(OH)2D3, while WU 515 contains an altered side chain with a 23-yne modification combined with hexafluorination at C-26 and C-27. Presently, it is unknown how the removal of C-ring from the CD-ring skeleton of 1alpha,25(OH)2D3 would affect its target tissue metabolism. In the present study, we compared the metabolic fate of SL 117 and WU 515 with that of 1alpha,25(OH)2D3 in both the isolated perfused rat kidney, which expresses only the C-24 oxidation pathway and rat osteosarcoma cells (UMR 106), which express both the C-24 oxidation and C-3 epimerization pathways. The results of our present study indicate that SL 117 is metabolized like 1alpha,25(OH)2D3, into polar metabolites via the C-24 oxidation pathway in both rat kidney and UMR 106 cells. As expected, WU 515 with altered side chain structure is not metabolized via the C-24 oxidation pathway. Unlike in rat kidney, both SL 117 and WU 515 are also metabolized into less polar metabolites in UMR 106 cells. These metabolites displayed GC and MS characteristics consistent with A-ring epimerization and were putatively assigned as C-3 epimers of SL 117 and WU 515. In summary, we report that removal of the C-ring from the CD-ring skeleton of 1alpha,25(OH)2D3 does not alter its target tissue metabolism significantly. 相似文献
102.
Fabrizio Briganti Demetrio Randazzo Andrea Scozzafava Debora Berti Piero Baglioni Patrizia Di Gennaro Enrica Galli Giuseppina Bestetti 《Journal of Molecular Catalysis .B, Enzymatic》1999,7(5-6):263-272
The whole cell biological conversion of naphthalene to (+)-cis-(1R,2S)-dihydroxy-1,2-dihydronaphthalene by the E. coli JM109(pPS1778) recombinant strain carrying the naphthalene dioxygenase and regulatory genes cloned from Pseudomonas fluorescens N3 in micellar systems has been investigated using biochemical and chemico-physical techniques. Reverse and direct micellar systems have been tested. Non-ionic surfactants (Tween and Triton X series) were found not to inhibit either the growth of the bacteria and the expression of the hydroxylating dioxygenase enzyme in such systems and were utilized in order to speed up the naphthalene conversion by increasing its solubility and also its bioavailability. The phase behavior of the direct micellar system was characterized through light scattering and other chemico-physical techniques. Further addition of isopropyl-palmitate 1–2% v/v to the micellar systems resulted in an increase of the apparent substrate concentration in solution and particularly its bioavailability thus allowing faster catalytic conversions resulting in an increase in productivity for the process. Since the cis-dihydrodiols are acquiring considerable potential as chiral pool synthons in asymmetric synthesis for a variety of industrial processes, possible applications for efficient small and large-scale production of such compounds are discussed. 相似文献
103.
Andrea Sacconi Claudia De Vitis Luisa de Latouliere Simona di Martino Francesca De Nicola Frauke Goeman Carla Mottini Francesca Paolini Michela DAscanio Alberto Ricci Agostino Tafuri Paolo Marchetti Arianna Di Napoli Luciano De Biase Andrea Negro Christian Napoli Paolo Anibaldi Valentina Salvati Darragh Duffy Benjamin Terrier Maurizio Fanciulli Carlo Capalbo Salvatore Sciacchitano Giovanni Blandino Giulia Piaggio Rita Mancini Gennaro Ciliberto 《Cell death & disease》2021,12(11)
104.
Barral DC Cavallari M McCormick PJ Garg S Magee AI Bonifacino JS De Libero G Brenner MB 《Traffic (Copenhagen, Denmark)》2008,9(9):1446-1457
CD1 proteins are a family of major histocompatibility complex (MHC) class I-like antigen-presenting molecules that present lipids to T cells. The cytoplasmic tails (CTs) of all human CD1 isoforms, with the exception of CD1a, contain tyrosine-based sorting motifs, responsible for the internalization of proteins by the clathrin-mediated pathway. The role of the CD1a CT, which does not possess any sorting motifs, as well as its mode of internalization are not known. We investigated the internalization and recycling pathways followed by CD1a and the role of its CT. We found that CD1a can be internalized by a clathrin- and dynamin-independent pathway and that it follows a Rab22a- and ADP ribosylation factor (ARF)6-dependent recycling pathway, similar to other cargo internalized independent of clathrin. We also found that the CD1a CT is S-acylated. However, this posttranslational modification does not determine the rate of internalization or recycling of the protein or its localization to detergent-resistant membrane microdomains (DRMs) where we found CD1a to be enriched. We also show that plasma membrane DRMs are essential for efficient CD1a-mediated antigen presentation. These findings place CD1a closer to MHC class I in its trafficking and potential antigen-loading compartments among CD1 isoforms. Furthermore, we identify CD1a as a new marker for the clathrin- and dynamin-independent and DRM-dependent pathway of internalization as well as the Rab22a- and ARF6-dependent recycling pathway. 相似文献
105.
The CD spectra of the series PhCH(Me)R, with R = Et (1), nPr (2), iPr (3), and tBu (4), are reported (1-3 for the first time) at room temperature in the 185-280 nm range and at 183 K. These purely hydrocarbon compounds represent the simplest chiral systems containing the phenyl chromophore and exhibit Cotton effects exclusively allied with the benzene transitions. The bands in 1La and 1Lb regions were checked against the available sector rules, with discordant outcomes. Time-dependent density-functional theory calculations, with various functionals and basis sets tested, correctly reproduced the prominent CD bands observed for 1-4. 相似文献
106.
Rym Zitari-Chatti Noureddine Chatti Domenico Fulgione Immacolata Caiazza Gennaro Aprea Ali Elouaer Khaled Said Teresa Capriglione 《Genetica》2009,136(3):439-447
In this study we analysed mitochondrial DNA variation in Penaeus kerathurus prawns collected from seven locations along a transect across the Siculo–Tunisian region in order to verify if any population
structuring exists over a limited geographical scale and to delineate the putative transition zone with sufficient accuracy.
Partial DNA sequences of COI and 16S genes were analysed. In contrast to the highly conservative 16S gene, the COI sequences
exhibited sufficient diversity for population analysis. The COI gene revealed low levels of haplotype and nucleotide diversities.
The size of the annual landings of this commercial species suggests large population sizes. Hence, the low genetic diversity
detected in this study could indicate a possible reduction in effective population sizes in the past. We detected significant
genetic differentiation between eastern and western populations likely due to restricted gene flow across the Siculo–Tunisian
boundary. We discuss the different evolutionary forces that may have shaped the genetic variation and suggest that the genetic
divide is probably maintained by present-day dispersal limitation.
R. Zitari-Chatti and N. Chatti are contributed equally to the work. 相似文献
107.
108.
Federico Fogolari Haritha Haridas Alessandra Corazza Paolo Viglino Davide Corà Michele Caselle Gennaro Esposito Luigi E Xodo 《BMC structural biology》2009,9(1):64-20
Background
Independent surveys of human gene promoter regions have demonstrated an overrepresentation of G3X n1G3X n2G3X n3G3 motifs which are known to be capable of forming intrastrand quadruple helix structures. In spite of the widely recognized importance of G-quadruplex structures in gene regulation and growing interest around this unusual DNA structure, there are at present only few such structures available in the Nucleic Acid Database. In the present work we generate by molecular modeling feasible G-quadruplex structures which may be useful for interpretation of experimental data. 相似文献109.
Synthesis and biological evaluation of alpha-galactosylceramide (KRN7000) and isoglobotrihexosylceramide (iGb3) 总被引:3,自引:0,他引:3
Xia C Yao Q Schümann J Rossy E Chen W Zhu L Zhang W De Libero G Wang PG 《Bioorganic & medicinal chemistry letters》2006,16(8):2195-2199
Glycoceramides can activate NKT cells by binding with CD1d to produce IFN-gamma, IL-4, and other cytokines. An efficient synthetic pathway for alpha-galactosylceramide (KRN7000) was established by coupling a protected galactose donor to a properly protected ceramide. During the investigation, it was discovered that when the ceramide was protected with benzyl groups, only beta-galactosylceramide was produced from the glycosylation reaction. In contrast, the ceramide with benzoyl protecting groups produced alpha-galactosylceramide. Isoglobotrihexosylceramide (iGb3) was prepared by glycosylation of Galalpha1-3Galbeta1-4Glc donor with 2-azido-sphingosine in high yield. Biological assays on the synthetic KRN7000 and iGb3 were performed using human and murine iNKT cell clones or hybridomas. 相似文献
110.
Giorgetti S Raimondi S Pagano K Relini A Bucciantini M Corazza A Fogolari F Codutti L Salmona M Mangione P Colombo L De Luigi A Porcari R Gliozzi A Stefani M Esposito G Bellotti V Stoppini M 《The Journal of biological chemistry》2011,286(3):2121-2131
The discovery of methods suitable for the conversion in vitro of native proteins into amyloid fibrils has shed light on the molecular basis of amyloidosis and has provided fundamental tools for drug discovery. We have studied the capacity of a small library of tetracycline analogues to modulate the formation or destructuration of β2-microglobulin fibrils. The inhibition of fibrillogenesis of the wild type protein was first established in the presence of 20% trifluoroethanol and confirmed under a more physiologic environment including heparin and collagen. The latter conditions were also used to study the highly amyloidogenic variant, P32G. The NMR analysis showed that doxycycline inhibits β2-microglobulin self-association and stabilizes the native-like species through fast exchange interactions involving specific regions of the protein. Cell viability assays demonstrated that the drug abolishes the natural cytotoxic activity of soluble β2-microglobulin, further strengthening a possible in vivo therapeutic exploitation of this drug. Doxycycline can disassemble preformed fibrils, but the IC(50) is 5-fold higher than that necessary for the inhibition of fibrillogenesis. Fibril destructuration is a dynamic and time-dependent process characterized by the early formation of cytotoxic protein aggregates that, in a few hours, convert into non-toxic insoluble material. The efficacy of doxycycline as a drug against dialysis-related amyloidosis would benefit from the ability of the drug to accumulate just in the skeletal system where amyloid is formed. In these tissues, the doxycycline concentration reaches values several folds higher than those resulting in inhibition of amyloidogenesis and amyloid destructuration in vitro. 相似文献