全文获取类型
收费全文 | 610篇 |
免费 | 53篇 |
国内免费 | 1篇 |
专业分类
664篇 |
出版年
2022年 | 6篇 |
2021年 | 12篇 |
2019年 | 9篇 |
2018年 | 5篇 |
2017年 | 8篇 |
2016年 | 9篇 |
2015年 | 27篇 |
2014年 | 20篇 |
2013年 | 24篇 |
2012年 | 36篇 |
2011年 | 40篇 |
2010年 | 16篇 |
2009年 | 33篇 |
2008年 | 22篇 |
2007年 | 36篇 |
2006年 | 24篇 |
2005年 | 34篇 |
2004年 | 26篇 |
2003年 | 19篇 |
2002年 | 32篇 |
2001年 | 16篇 |
2000年 | 9篇 |
1999年 | 13篇 |
1998年 | 10篇 |
1997年 | 8篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1994年 | 7篇 |
1993年 | 12篇 |
1992年 | 7篇 |
1991年 | 4篇 |
1990年 | 6篇 |
1989年 | 4篇 |
1988年 | 5篇 |
1987年 | 4篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 4篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 4篇 |
1971年 | 5篇 |
1970年 | 5篇 |
1969年 | 4篇 |
1968年 | 4篇 |
1967年 | 3篇 |
1966年 | 3篇 |
1963年 | 3篇 |
1955年 | 3篇 |
排序方式: 共有664条查询结果,搜索用时 9 毫秒
171.
Teresa Cristina Leandro de Jesus Renata Rosito Tonelli Sheila C. Nardelli Leonardo da Silva Augusto Maria Cristina M. Motta Wendell Girard-Dias Kildare Miranda Paul Ulrich Veronica Jimenez Antonio Barquilla Miguel Navarro Roberto Docampo Sergio Schenkman 《The Journal of biological chemistry》2010,285(31):24131-24140
Target of rapamycin (TOR) kinases are highly conserved protein kinases that integrate signals from nutrients and growth factors to coordinate cell growth and cell cycle progression. It has been previously described that two TOR kinases control cell growth in the protozoan parasite Trypanosoma brucei, the causative agent of African trypanosomiasis. Here we studied an unusual TOR-like protein named TbTOR-like 1 containing a PDZ domain and found exclusively in kinetoplastids. TbTOR-like 1 localizes to unique cytosolic granules. After hyperosmotic stress, the localization of the protein shifts to the cell periphery, different from other organelle markers. Ablation of TbTOR-like 1 causes a progressive inhibition of cell proliferation, producing parasites accumulating in the S/G2 phase of the cell cycle. TbTOR-like 1 knocked down cells have an increased area occupied by acidic vacuoles, known as acidocalcisomes, and are enriched in polyphosphate and pyrophosphate. These results suggest that TbTOR-like 1 might be involved in the control of acidocalcisome and polyphosphate metabolism in T. brucei. 相似文献
172.
Taiana Haag Anelisie S. Santos Fernanda P. Valdez Dênis A. Sana Leandro Silveira Laury Cullen Jr. Carlos De Angelo Ronaldo G. Morato Peter G. Crawshaw Jr. Francisco M. Salzano Eduardo Eizirik 《Conservation Genetics》2010,11(3):1239-1242
Major evolutionary questions remain elusive due to persistent difficulties in directly studying the genetics of variable phenotypes in natural populations. Many phenotypic variants may be of adaptive relevance, and thus important to consider in the context of conservation genetics. However, since the dynamics of these traits is usually poorly understood in the wild, their incorporation in conservation strategies is difficult to accomplish. For animals which exhibit intriguing phenotypic variation but are difficult to track in the wild, innovative approaches are required to investigate such issues. Here we demonstrate that non-invasive DNA sampling can be used to study the genetics and ecology of melanism in the jaguar, by directly genotyping the molecular polymorphism underlying this coloration trait. These results open new prospects for the in-depth investigation of this polymorphism, and highlight the broader potential of non-invasive DNA-based phenotype tracking for wildlife in general. 相似文献
173.
The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements 总被引:2,自引:0,他引:2
MAQC Consortium Shi L Reid LH Jones WD Shippy R Warrington JA Baker SC Collins PJ de Longueville F Kawasaki ES Lee KY Luo Y Sun YA Willey JC Setterquist RA Fischer GM Tong W Dragan YP Dix DJ Frueh FW Goodsaid FM Herman D Jensen RV Johnson CD Lobenhofer EK Puri RK Schrf U Thierry-Mieg J Wang C Wilson M Wolber PK Zhang L Amur S Bao W Barbacioru CC Lucas AB Bertholet V Boysen C Bromley B Brown D Brunner A Canales R Cao XM Cebula TA Chen JJ Cheng J Chu TM Chudin E Corson J Corton JC Croner LJ 《Nature biotechnology》2006,24(9):1151-1161
Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. 相似文献
174.
Shippy R Fulmer-Smentek S Jensen RV Jones WD Wolber PK Johnson CD Pine PS Boysen C Guo X Chudin E Sun YA Willey JC Thierry-Mieg J Thierry-Mieg D Setterquist RA Wilson M Lucas AB Novoradovskaya N Papallo A Turpaz Y Baker SC Warrington JA Shi L Herman D 《Nature biotechnology》2006,24(9):1123-1131
We have assessed the utility of RNA titration samples for evaluating microarray platform performance and the impact of different normalization methods on the results obtained. As part of the MicroArray Quality Control project, we investigated the performance of five commercial microarray platforms using two independent RNA samples and two titration mixtures of these samples. Focusing on 12,091 genes common across all platforms, we determined the ability of each platform to detect the correct titration response across the samples. Global deviations from the response predicted by the titration ratios were observed. These differences could be explained by variations in relative amounts of messenger RNA as a fraction of total RNA between the two independent samples. Overall, both the qualitative and quantitative correspondence across platforms was high. In summary, titration samples may be regarded as a valuable tool, not only for assessing microarray platform performance and different analysis methods, but also for determining some underlying biological features of the samples. 相似文献
175.
Kimberly Y. Epps Nicholas B. Comerford James B. Reeves III Wendell P. Cropper Jr. Quintino R. Araujo 《Oikos》2007,116(11):1831-1840
The lack of predictability in litter-mix studies may result from the low correlation between species number and the traits that drive the processes under observation. From the standpoint of litter-quality-dependent ecological processes, we propose that litter chemical qualities are functional traits and introduce a multivariate index of chemical diversity (CDQ ) based on Rao's quadratic entropy to describe the compositional heterogeneity of litter and foliar mixtures. Using published data from temperate and tropical forest systems to illustrate the relationship between species richness and chemical diversity, we show the variation of chemical diversity based on profiles of total nutrient concentrations (N, P, K, Ca and Mg) with species richness. We discuss how this behavior may explain the idiosyncratic responses exhibited in litter-mix experiments and how it may contribute to the observed dominance of species identity over species diversity. As a summary of resource heterogeneity relevant to detritivore and microbial processes, the chemical diversity index is potentially a better predictor of diversity effects on nutrient dynamics than species richness. Finally, we propose the use of infrared spectroscopy techniques for a rapid and more comprehensive determination of foliar and litter chemical composition to provide a more information-rich index. 相似文献
176.
Echinococcus granulosus larvae secret a polymeric lipoprotein known as antigen B (AgB) into the metacestode hydatid fluid. Three similar AgB subunits have been previously identified (AgB1, AgB2, and AgB3), and their respective genes isolated, but the actual number of genes encoding AgB subunits remains uncertain. In this study, we characterize the variability of genes encoding the AgB2 subunit, using PCR and RT-PCR followed by cloning and sequencing. We have analyzed 32 cDNA and 34 genomic sequences from a single metacestode, showing a high degree of sequence polymorphism. In addition, we have identified a possibly new AgB subunit, which we call AgB4. Additionally, we describe an AgB2 genomic clone lacking (i) a segment corresponding to the intron and (ii) a short, 45 bp sequence within exon II. The 45 bp segment encompasses the conserved splicing signals and corresponds to a highly conserved insect promoter motif. 相似文献
177.
Haag CR Sakwińska O Ebert D 《Evolution; international journal of organic evolution》2003,57(4):777-783
Abstract It has been proposed that parasitic infections increase selection against inbred genotypes. We tested this hypothesis experimentally using pairs of selfed and outcrossed sibling lines of the freshwater crustacean Daphnia magna , which can be maintained clonally. We studied the performance of selfed relative to outcrossed sibling clones during repeated pairwise clonal competition in the presence and absence of two species of microsporidian parasites. In 13 of the 14 pairs, the selfed clones did worse than the outcrossed ones in the control treatment, but the presence of either parasite did not result in an overall increase in this difference. Rather, it decreased the performance of the selfed relative to the outcrossed sibling in some pairs and increased it in others. Moreover, the two parasite species did not have the same effect in a given pair. This indicates that, contrary to the hypothesis that parasites generally lead to a decreased performance of inbred genotypes, their effect may depend on the genetic background of the host as well as on the parasite species, and suggests that inbreeding can lead to reduced or increased resistance to parasites. Our findings also indicate that there is variation for specific resistance to different species of parasites in the meta-population from which the hosts for this study were obtained. 相似文献
178.
Krebs C Koestner W Nissen M Welge V Parusel I Malavasi F Leiter EH Santella RM Haag F Koch-Nolte F 《Analytical biochemistry》2003,314(1):108-115
NAD-dependent ADP-ribosylation is one of the posttranslational protein modifications. On mammalian cells, glycosylphosphatidylinositol-anchored cell surface ADP-ribosyltransferases (ARTs) ADP-ribosylate other cell surface proteins and thereby affect important cellular functions. Here we describe convenient flow-cytometric and immunoblot assays for monitoring ADP-ribosylation of cell surface proteins on living cells by exploiting the capacity of ARTs to utilize etheno-NAD as substrate. Etheno-ADP-ribosylation of cell surface proteins can be detected by flow cytometry with 1G4, a monoclonal antibody specific for ethenoadenosine. Labeling of cells with 1G4 is dependent on the expression of cell surface ARTs and occurs only after incubation of ART-expressing cells with etheno-NAD and not with etheno-ADP-ribose. Dose-response analyses show efficient 1G4 staining of ART-expressing cells at micromolar etheno-NAD concentrations. Half-maximal staining is obtained with 1-2 micro M etheno-NAD, saturation is reached at 5-20 micro M etheno-NAD. Immunoblot analyses confirm that ART-expressing cells incorporate ethenoadenosine covalently (i.e., SDS resistant) into several cell surface proteins. The flow-cytometric 1G4 staining assay can be used to identify subpopulations of cells expressing cell surface ART activity and to select ART(hi) cell variants. The immunoblot 1G4 staining assay can also be used to identify etheno-ADP-ribosylated target proteins. These new assays hold promise for many interesting applications in biochemistry and cell biology. 相似文献
179.
180.
Glowacki G Braren R Firner K Nissen M Kühl M Reche P Bazan F Cetkovic-Cvrlje M Leiter E Haag F Koch-Nolte F 《Protein science : a publication of the Protein Society》2002,11(7):1657-1670
ADP-ribosyltransferases including toxins secreted by Vibrio cholera, Pseudomonas aerurginosa, and other pathogenic bacteria inactivate the function of human target proteins by attaching ADP-ribose onto a critical amino acid residue. Cross-species polymerase chain reaction (PCR) and database mining identified the orthologs of these ADP-ribosylating toxins in humans and the mouse. The human genome contains four functional toxin-related ADP-ribosyltransferase genes (ARTs) and two related intron-containing pseudogenes; the mouse has six functional orthologs. The human and mouse ART genes map to chromosomal regions with conserved linkage synteny. The individual ART genes reveal highly restricted expression patterns, which are largely conserved in humans and the mouse. We confirmed the predicted extracellular location of the ART proteins by expressing recombinant ARTs in insect cells. Two human and four mouse ARTs contain the active site motif (R-S-EXE) typical of arginine-specific ADP-ribosyltransferases and exhibit the predicted enzyme activities. Two other human ARTs and their murine orthologues deviate in the active site motif and lack detectable enzyme activity. Conceivably, these ARTs may have acquired a new specificity or function. The position-sensitive iterative database search program PSI-BLAST connected the mammalian ARTs with most known bacterial ADP-ribosylating toxins. In contrast, no related open reading frames occur in the four completed genomes of lower eucaryotes (yeast, worm, fly, and mustard weed). Interestingly, these organisms also lack genes for ADP-ribosylhydrolases, the enzymes that reverse protein ADP-ribosylation. This suggests that the two enzyme families that catalyze reversible mono-ADP-ribosylation either were lost from the genomes of these nonchordata eucaryotes or were subject to horizontal gene transfer between kingdoms. 相似文献