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51.
Mature dendritic cells infected with herpes simplex virus type 1 exhibit inhibited T-cell stimulatory capacity 总被引:22,自引:0,他引:22
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Kruse M Rosorius O Krätzer F Stelz G Kuhnt C Schuler G Hauber J Steinkasserer A 《Journal of virology》2000,74(15):7127-7136
Mature dendritic cells (DC) are the most potent antigen-presenting cells within the entire immune system. Interference with the function of these cells therefore constitutes a very powerful mechanism for viruses to escape immune responses. Several members of the Herpesviridae family have provided examples of such escape strategies, including interference with antigen presentation and production of homologous cytokines. In this study we investigated the infection of mature DC with herpes simplex virus type 1 (HSV-1) and the way in which infection alters the phenotype and function of mature DC. Interestingly, the T-cell-stimulatory capacity of these DC was strongly impaired. Furthermore, we demonstrated that HSV-1 leads to the specific degradation of CD83, a cell surface molecule which is specifically upregulated during DC maturation. These data indicate that HSV-1 has developed yet another novel mechanism to escape immune responses. 相似文献
52.
M M Nthen S Cichon I R Vogt S Hemmer R Kruse M Knapp T Hller M Faiyaz ul Haque S Haque P Propping M Ahmad M Rietschel 《American journal of human genetics》1998,62(2):386-390
Complete or partial congenital absence of hair (congenital alopecia) may occur either in isolation or with associated defects. The majority of families with isolated congenital alopecia has been reported to follow an autosomal-recessive mode of inheritance (MIM 203655). As yet, no gene has been linked to isolated congenital alopecia, nor has linkage been established to a specific region of the genome. In an attempt to map the gene for the autosomal recessive form of the disorder, we have performed genetic linkage analysis on a large inbred Pakistani family in which affected persons show complete absence of hair development (universal congenital alopecia). We have analyzed individuals of this family, using >175 microsatellite polymorphic markers of the human genome. A maximum LOD score of 7.90 at a recombination fraction of 0 has been obtained with locus D8S258. Haplotype analysis of recombination events localized the disease to a 15-cM region between marker loci D8S261 and D8S1771. We have thus mapped the gene for this hereditary form of isolated congenital alopecia to a locus on chromosome 8p21-22 (ALUNC [alopecia universalis congenitalis]). This will aid future identification of the responsible gene, which will be extremely useful for the understanding of the biochemistry of hair development. 相似文献
53.
Data from interlaboratory surveys for the determination of CA 125 (1987 to 1998) show large differences depending on the commercial kit used. Samples of the same material produced different analytical results in different interlaboratory surveys, thus showing that some kits did not have a satisfactory rate of reproducibility over a longer period of time. 相似文献
54.
Francesca Luciani Sara Galluzzo Andrea Gaggioli Nanna Aaby Kruse Pascal Venneugues Christian K Schneider Carlo Pini Daniela Melchiorri 《MABS-AUSTIN》2015,7(3):451-455
Quality by design (QbD) is an innovative approach to drug development that has started to be implemented into the regulatory framework, but currently mainly for chemical drugs. The recent marketing authorization of the first monoclonal antibody developed using extensive QbD concepts in the European Union paves the way for future further regulatory approvals of complex products employing this cutting-edge technological concept. In this paper, we report and comment on insights and lessons learnt from the non-public discussions in the European Medicines Agency''s Biologicals Working Party and Committee for Medicinal Products for Human Use on the key issues during evaluation related to the implementation of an extensive QbD approach for biotechnology-derived medicinal products. Sharing these insights could prove useful for future developments in QbD for biotech products in general and monoclonal antibodies in particular. 相似文献
55.
56.
Certain combinations of the killer immunoglobulin-like receptors (KIR) and major histocompatibility complex class I ligands
in humans predispose carriers to a variety of diseases, requiring sophisticated genotyping of the highly polymorphic and diverse
KIR and HLA genes. Particularly, KIR genotyping is challenging due to polymorphisms (allelic substitutions), genomic diversity (presence/absence of genes), and
frequent duplications. Rhesus macaques are often used as important animal models of human diseases such as, e.g. AIDS. However,
typing of rhesus macaque KIR genes has not been described so far. In this study, we report the identification of additional novel rhesus macaque KIR cDNA sequences and a sequence-specific KIR genotyping assay. From a cohort of four rhesus macaque families with a total of 70 individuals, we identified 25 distinct
KIR genotypes. Segregation analyses of KIR genes and of two polymorphic microsatellite markers allowed the identification of 21 distinct KIR haplotypes in these families, with five to 11 segregating KIR genes per haplotype. Our analyses confirmed and extended knowledge on differential gene KIR gene content in macaques and indicate that rhesus macaque and human KIR haplotypes show a comparable level of diversity and complexity. 相似文献
57.
Chae PS Rasmussen SG Rana RR Gotfryd K Chandra R Goren MA Kruse AC Nurva S Loland CJ Pierre Y Drew D Popot JL Picot D Fox BG Guan L Gether U Byrne B Kobilka B Gellman SH 《Nature methods》2010,7(12):1003-1008
The understanding of integral membrane protein (IMP) structure and function is hampered by the difficulty of handling these proteins. Aqueous solubilization, necessary for many types of biophysical analysis, generally requires a detergent to shield the large lipophilic surfaces of native IMPs. Many proteins remain difficult to study owing to a lack of suitable detergents. We introduce a class of amphiphiles, each built around a central quaternary carbon atom derived from neopentyl glycol, with hydrophilic groups derived from maltose. Representatives of this maltose-neopentyl glycol (MNG) amphiphile family show favorable behavior relative to conventional detergents, as manifested in multiple membrane protein systems, leading to enhanced structural stability and successful crystallization. MNG amphiphiles are promising tools for membrane protein science because of the ease with which they may be prepared and the facility with which their structures may be varied. 相似文献
58.
Jos H.M. Lange Martina A.W. van der Neut Arnold P. den Hartog Henri C. Wals Jan Hoogendoorn Herman H. van Stuivenberg Bernard J. van Vliet Chris G. Kruse 《Bioorganic & medicinal chemistry letters》2010,20(5):1752-1757
The synthesis, structure–activity relationship (SAR) studies and intramolecular hydrogen bonding pattern of 1,3,5-trisubstituted 4,5-dihydropyrazoles are described. The target compounds 6–18 represent a novel class of potent and selective CB1 receptor antagonists. Based on X-ray diffraction data, the orally active 17 is shown to elicit a different intramolecular H-bonding mode as compared to ibipinabant (3) and SLV330 (4). 相似文献
59.
Quantitative chemical proteomics reveals mechanisms of action of clinical ABL kinase inhibitors 总被引:8,自引:0,他引:8
Bantscheff M Eberhard D Abraham Y Bastuck S Boesche M Hobson S Mathieson T Perrin J Raida M Rau C Reader V Sweetman G Bauer A Bouwmeester T Hopf C Kruse U Neubauer G Ramsden N Rick J Kuster B Drewes G 《Nature biotechnology》2007,25(9):1035-1044
We describe a chemical proteomics approach to profile the interaction of small molecules with hundreds of endogenously expressed protein kinases and purine-binding proteins. This subproteome is captured by immobilized nonselective kinase inhibitors (kinobeads), and the bound proteins are quantified in parallel by mass spectrometry using isobaric tags for relative and absolute quantification (iTRAQ). By measuring the competition with the affinity matrix, we assess the binding of drugs to their targets in cell lysates and in cells. By mapping drug-induced changes in the phosphorylation state of the captured proteome, we also analyze signaling pathways downstream of target kinases. Quantitative profiling of the drugs imatinib (Gleevec), dasatinib (Sprycel) and bosutinib in K562 cells confirms known targets including ABL and SRC family kinases and identifies the receptor tyrosine kinase DDR1 and the oxidoreductase NQO2 as novel targets of imatinib. The data suggest that our approach is a valuable tool for drug discovery. 相似文献
60.
Spatio-temporal oscillations of the Min proteins are essential for selecting the cell division site in Escherichia coli. These oscillations are a key example of a biological phenomenon that can only be understood on a systems level rather than on the level of its individual components. Here, we review the key concepts that mathematical modelling has added to our understanding of the Min system. While several different mechanisms have been proposed, in all cases the oscillations emerge from a dynamic instability of a uniform protein distribution. To generate this instability, however, the various mechanisms rely on different features of Min protein interactions and transport. We critically evaluate these mechanisms in light of recent experimental evidence. We also review the effects of fluctuations caused by low cellular concentration of Min proteins, and describe how stochastic effects may potentially influence Min protein dynamics. 相似文献