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排序方式: 共有159条查询结果,搜索用时 15 毫秒
81.
The BEACH protein LRBA is required for hair bundle maintenance in cochlear hair cells and for hearing 下载免费PDF全文
Christian Vogl Tanvi Butola Natja Haag Torben J Hausrat Michael G Leitner Michel Moutschen Philippe P Lefèbvre Carsten Speckmann Lillian Garrett Lore Becker Helmut Fuchs Martin Hrabe de Angelis Sandor Nietzsche Michael M Kessels Dominik Oliver Matthias Kneussel Nicola Strenzke 《EMBO reports》2017,18(11):2015-2029
Lipopolysaccharide‐responsive beige‐like anchor protein (LRBA) belongs to the enigmatic class of BEACH domain‐containing proteins, which have been attributed various cellular functions, typically involving intracellular protein and membrane transport processes. Here, we show that LRBA deficiency in mice leads to progressive sensorineural hearing loss. In LRBA knockout mice, inner and outer hair cell stereociliary bundles initially develop normally, but then partially degenerate during the second postnatal week. LRBA deficiency is associated with a reduced abundance of radixin and Nherf2, two adaptor proteins, which are important for the mechanical stability of the basal taper region of stereocilia. Our data suggest that due to the loss of structural integrity of the central parts of the hair bundle, the hair cell receptor potential is reduced, resulting in a loss of cochlear sensitivity and functional loss of the fraction of spiral ganglion neurons with low spontaneous firing rates. Clinical data obtained from two human patients with protein‐truncating nonsense or frameshift mutations suggest that LRBA deficiency may likewise cause syndromic sensorineural hearing impairment in humans, albeit less severe than in our mouse model. 相似文献
82.
Nguyen HP Seto NO MacKenzie CR Brade L Kosma P Brade H Evans SV 《Nature structural biology》2003,10(12):1019-1025
High-resolution structures reveal how a germline antibody can recognize a range of clinically relevant carbohydrate epitopes. The germline response to a carbohydrate immunogen can be critical to survivability, with selection for antibody gene segments that both confer protection against common pathogens and retain the flexibility to adapt to new disease organisms. We show here that antibody S25-2 binds several distinct inner-core epitopes of bacterial lipopolysaccharides (LPSs) by linking an inherited monosaccharide residue binding site with a subset of complementarity-determining regions (CDRs) of limited flexibility positioned to recognize the remainder of an array of different epitopes. This strategy allows germline antibodies to adapt to different epitopes while minimizing entropic penalties associated with the immobilization of labile CDRs upon binding of antigen, and provides insight into the link between the genetic origin of individual CDRs and their respective roles in antigen recognition. 相似文献
83.
A single nucleotide exchange in the wzy gene is responsible for the semirough O6 lipopolysaccharide phenotype and serum sensitivity of Escherichia coli strain Nissle 1917 总被引:1,自引:0,他引:1 下载免费PDF全文
Grozdanov L Zähringer U Blum-Oehler G Brade L Henne A Knirel YA Schombel U Schulze J Sonnenborn U Gottschalk G Hacker J Rietschel ET Dobrindt U 《Journal of bacteriology》2002,184(21):5912-5925
Structural analysis of lipopolysaccharide (LPS) isolated from semirough, serum-sensitive Escherichia coli strain Nissle 1917 (DSM 6601, serotype O6:K5:H1) revealed that this strain's LPS contains a bisphosphorylated hexaacyl lipid A and a tetradecasaccharide consisting of one E. coli O6 antigen repeating unit attached to the R1-type core. Configuration of the GlcNAc glycosidic linkage between O-antigen oligosaccharide and core (beta) differs from that interlinking the repeating units in the E. coli O6 antigen polysaccharide (alpha). The wa(*) and wb(*) gene clusters of strain Nissle 1917, required for LPS core and O6 repeating unit biosyntheses, were subcloned and sequenced. The DNA sequence of the wa(*) determinant (11.8 kb) shows 97% identity to other R1 core type-specific wa(*) gene clusters. The DNA sequence of the wb(*) gene cluster (11 kb) exhibits no homology to known DNA sequences except manC and manB. Comparison of the genetic structures of the wb(*)(O6) (wb(*) from serotype O6) determinants of strain Nissle 1917 and of smooth and serum-resistant uropathogenic E. coli O6 strain 536 demonstrated that the putative open reading frame encoding the O-antigen polymerase Wzy of strain Nissle 1917 was truncated due to a point mutation. Complementation with a functional wzy copy of E. coli strain 536 confirmed that the semirough phenotype of strain Nissle 1917 is due to the nonfunctional wzy gene. Expression of a functional wzy gene in E. coli strain Nissle 1917 increased its ability to withstand antibacterial defense mechanisms of blood serum. These results underline the importance of LPS for serum resistance or sensitivity of E. coli. 相似文献
84.
Göggel R Winoto-Morbach S Vielhaber G Imai Y Lindner K Brade L Brade H Ehlers S Slutsky AS Schütze S Gulbins E Uhlig S 《Nature medicine》2004,10(2):155-160
Platelet-activating factor (PAF) induces pulmonary edema and has a key role in acute lung injury (ALI). Here we show that PAF induces pulmonary edema through two mechanisms: acid sphingomyelinase (ASM)-dependent production of ceramide, and activation of the cyclooxygenase pathway. Agents that interfere with PAF-induced ceramide synthesis, such as steroids or the xanthogenate D609, attenuate pulmonary edema formation induced by PAF, endotoxin or acid instillation. Our results identify acid sphingomyelinase and ceramide as possible therapeutic targets in acute lung injury. 相似文献
85.
Simone Esposito Koen Deventer Lore Geldof Peter Van Eenoo 《Journal of peptide science》2015,21(1):1-9
Peptide hormones represent an emerging class of potential doping agents. Detection of their misuse is difficult due to their short half‐life in plasma and rapid elimination. Therefore, investigating their metabolism can improve detectability. Unfortunately, pharmacokinetic studies with human volunteers are often not allowed because of ethical constraints, and therefore alternative models are needed. This study was performed in order to evaluate in vitro models (human liver microsomes and S9 fraction) for the prediction of the metabolism of peptidic doping agents and to compare them with the established models. The peptides that were investigated include desmopressin, TB‐500, GHRP‐2, GHRP‐6, hexarelin, LHRH and leuprolide. Several metabolites were detected for each peptide after incubation with human liver microsomes, S9 fraction, and serum, which all showed endopeptidase and exopeptidase activity. In vitro models from different organs (liver vs. kidney) were compared, but no significant differences were recorded. Deamidation was not observed in any of the models and was therefore evaluated by incubation with α‐chymotrypsin. In conclusion, in vitro models are useful tools for forensic and clinical analysts to detect peptidic metabolic markers in biological fluids. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
86.
Energy potential for combustion and anaerobic digestion of biomass from low-input high-diversity systems in conservation areas 下载免费PDF全文
Koenraad Van Meerbeek Lise Appels Raf Dewil Jonathan Van Beek Lore Bellings Kenny Liebert Bart Muys Martin Hermy 《Global Change Biology Bioenergy》2015,7(4):888-898
In this study, we assessed the potential for bioenergy production of Low-Input High-Diversity (LIHD) systems in temperate West-European conservation areas. A wide range of seminatural ecosystems (wet and dry grasslands, marshes, tall-herb vegetation and heathlands) was sampled. Because LIHD biomass is often scattered and discontinuously available, we only considered the potential for anaerobic digestion and combustion. Both technologies are suitable for decentralized biomass utilization. The gross energy yield showed a promising range between 46–277 GJ per hectare per mowing cycle (MC). The energy efficiency of the anaerobic digestion process was rather low (10–30%) with a methane energy yield of 5.5–35.5 GJ ha−1 MC−1, experimentally determined by batch digestion tests. The water content, functional group composition and biochemical composition (hemicellulose, cellulose, lignin and Kjeldahl nitrogen) of the biomass were analyzed to assess the suitability of different valorization pathways. On the basis of the results, we were able to propose recommendations regarding the appropriate conversion techniques. Biomass from plant communities with ‘late’ harvest dates (August–October) or a high fraction of woody species like heathland and dune slacks, is best valorized through combustion, while herbaceous biomass of ‘early’ harvested grasslands (June–July) and tall-herb vegetation can better be digested. The main advantages of the production of bioenergy from LIHD biomass originating from conservation management are the minimization of the competition with food production and its potential to reconcile renewable energy policies and biodiversity goals. 相似文献
87.
88.
Ushio Fujikura Lore Elsaesser Holger Breuninger Clara Sánchez-Rodríguez Alexander Ivakov Thomas Laux Kim Findlay Staffan Persson Michael Lenhard 《PLoS genetics》2014,10(9)
Growth of plant organs relies on cell proliferation and expansion. While an increasingly detailed picture about the control of cell proliferation is emerging, our knowledge about the control of cell expansion remains more limited. We demonstrate here that the internal-motor kinesin AtKINESIN-13A (AtKIN13A) limits cell expansion and cell size in Arabidopsis thaliana, with loss-of-function atkin13a mutants forming larger petals with larger cells. The homolog, AtKINESIN-13B, also affects cell expansion and double mutants display growth, gametophytic and early embryonic defects, indicating a redundant role of the two genes. AtKIN13A is known to depolymerize microtubules and influence Golgi motility and distribution. Consistent with this function, AtKIN13A interacts genetically with ANGUSTIFOLIA, encoding a regulator of Golgi dynamics. Reduced AtKIN13A activity alters cell wall structure as assessed by Fourier-transformed infrared-spectroscopy and triggers signalling via the THESEUS1-dependent cell-wall integrity pathway, which in turn promotes the excess cell expansion in the atkin13a mutant. Thus, our results indicate that the intracellular activity of AtKIN13A regulates cell expansion and wall architecture via THESEUS1, providing a compelling case of interplay between cell wall integrity sensing and expansion. 相似文献
89.
Alexander F. Keist Florentina Ferchiu Lea Sante Sebastian Frese Wilhelm Bloch Florian Kreppel Stefan Kochanek Anca Sindrilaru Sebastian Iben Josef Högel Michael Ohnmacht Lutz E. Claes Anita Ignatius Jin Ho Chung Min Jung Lee York Kamenisch Mark Berneburg Thorsten Nikolaus Kerstin E. Braunstein Anne‐Dorte Sperfeld Albert C. Ludolph Karlis Briviba Meinhard Wlaschek Lore Florin Peter Angel Karin Scharffetter‐Kochanek 《Aging cell》2011,10(5):912-912
90.