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排序方式: 共有695条查询结果,搜索用时 15 毫秒
101.
Tjakko J. van Ham Karen L. Thijssen Rainer Breitling Robert M. W. Hofstra Ronald H. A. Plasterk Ellen A. A. Nollen 《PLoS genetics》2008,4(3)
Inclusions in the brain containing α-synuclein are the pathological hallmark of Parkinson''s disease, but how these inclusions are formed and how this links to disease is poorly understood. We have developed a C. elegans model that makes it possible to monitor, in living animals, the formation of α-synuclein inclusions. In worms of old age, inclusions contain aggregated α- synuclein, resembling a critical pathological feature. We used genome-wide RNA interference to identify processes involved in inclusion formation, and identified 80 genes that, when knocked down, resulted in a premature increase in the number of inclusions. Quality control and vesicle-trafficking genes expressed in the ER/Golgi complex and vesicular compartments were overrepresented, indicating a specific role for these processes in α-synuclein inclusion formation. Suppressors include aging-associated genes, such as sir-2.1/SIRT1 and lagr-1/LASS2. Altogether, our data suggest a link between α-synuclein inclusion formation and cellular aging, likely through an endomembrane-related mechanism. The processes and genes identified here present a framework for further study of the disease mechanism and provide candidate susceptibility genes and drug targets for Parkinson''s disease and other α-synuclein related disorders. 相似文献
102.
Propagation of protein glycation damage involves modification of tryptophan residues via reactive oxygen species: inhibition by pyridoxamine 总被引:3,自引:1,他引:2
Chetyrkin SV Mathis ME Ham AJ Hachey DL Hudson BG Voziyan PA 《Free radical biology & medicine》2008,44(7):1276-1285
Nonenzymatic modification of proteins is one of the key pathogenic factors in diabetic complications. Uncovering the mechanisms of protein damage caused by glucose is fundamental to understanding this pathogenesis and in the development of new therapies. We investigated whether the mechanism involving reactive oxygen species can propagate protein damage in glycation reactions beyond the classical modifications of lysine and arginine residues. We have demonstrated that glucose can cause specific oxidative modification of tryptophan residues in lysozyme and inhibit lysozyme activity. Furthermore, modification of tryptophan residues was also induced by purified albumin-Amadori, a ribose-derived model glycation intermediate. The AGE inhibitor pyridoxamine (PM) prevented the tryptophan modification, whereas another AGE inhibitor and strong carbonyl scavenger, aminoguanidine, was ineffective. PM specifically inhibited generation of hydroxyl radical from albumin-Amadori and protected tryptophan from oxidation by hydroxyl radical species. We conclude that oxidative degradation of either glucose or the protein-Amadori intermediate causes oxidative modification of protein tryptophan residues via hydroxyl radical and can affect protein function under physiologically relevant conditions. This oxidative stress-induced structural and functional protein damage can be ameliorated by PM via sequestration of catalytic metal ions and scavenging of hydroxyl radical, a mechanism that may contribute to the reported therapeutic effects of PM in the complications of diabetes. 相似文献
103.
Sander A. Peters Erwin Datema Dóra Szinay Marjo J. van Staveren Elio G.W.M. Schijlen Jan C. van Haarst Thamara Hesselink Marleen H.C. Abma-Henkens Yuling Bai Hans de Jong Willem J. Stiekema René M. Klein Lankhorst Roeland C.H.J. van Ham 《The Plant journal : for cell and molecular biology》2009,58(5):857-869
104.
Edward T. Mee Neil Berry Claire Ham Ulrike Sauermann Maria T. Maggiorella Frédéric Martinon Ernst J. Verschoor Jonathan L. Heeney Roger Le Grand Fausto Titti Neil Almond Nicola J. Rose 《Immunogenetics》2009,61(5):327-339
The restricted diversity of the major histocompatibility complex (MHC) of Mauritian cynomolgus macaques provides powerful
opportunities for insight into host-viral interactions and cellular immune responses that restrict lentiviral infections.
However, little is known about the effects of Mhc haplotypes on control of SIV in this species. Using microsatellite-based
genotyping and allele-specific PCR, Mhc haplotypes were deduced for 35 macaques infected with the same stock of SIVmac251.
Class I haplotype H6 was associated with a reduction in chronic phase viraemia (p = 0.0145) while a similar association was observed for H6 class II (p = 0.0063). An increase in chronic phase viraemia, albeit an insignificant trend, was observed in haplotype H5-positive animals.
These results further emphasise the value of genetically defined populations of non-human primates in AIDS research and provide
a foundation for detailed characterisation of MHC restricted cellular immune responses and the effects of host genetics on
SIV replication in cynomolgus macaques.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
105.
Drabek K van Ham M Stepanova T Draegestein K van Horssen R Sayas CL Akhmanova A Ten Hagen T Smits R Fodde R Grosveld F Galjart N 《Current biology : CB》2006,16(22):2259-2264
In motile fibroblasts, stable microtubules (MTs) are oriented toward the leading edge of cells. How these polarized MT arrays are established and maintained, and the cellular processes they control, have been the subject of many investigations. Several MT "plus-end-tracking proteins," or +TIPs, have been proposed to regulate selective MT stabilization, including the CLASPs, a complex of CLIP-170, IQGAP1, activated Cdc42 or Rac1, a complex of APC, EB1, and mDia1, and the actin-MT crosslinking factor ACF7. By using mouse embryonic fibroblasts (MEFs) in a wound-healing assay, we show here that CLASP2 is required for the formation of a stable, polarized MT array but that CLIP-170 and an APC-EB1 interaction are not essential. Persistent motility is also hampered in CLASP2-deficient MEFs. We find that ACF7 regulates cortical CLASP localization in HeLa cells, indicating it acts upstream of CLASP2. Fluorescence-based approaches show that GFP-CLASP2 is immobilized in a bimodal manner in regions near cell edges. Our results suggest that the regional immobilization of CLASP2 allows MT stabilization and promotes directionally persistent motility in fibroblasts. 相似文献
106.
Yiannis A. I. Kourmpetis Aalt D. J. van Dijk Marco C. A. M. Bink Roeland C. H. J. van Ham Cajo J. F. ter Braak 《PloS one》2010,5(2)
Inference of protein functions is one of the most important aims of modern
biology. To fully exploit the large volumes of genomic data typically produced
in modern-day genomic experiments, automated computational methods for protein
function prediction are urgently needed. Established methods use sequence or
structure similarity to infer functions but those types of data do not suffice
to determine the biological context in which proteins act. Current
high-throughput biological experiments produce large amounts of data on the
interactions between proteins. Such data can be used to infer interaction
networks and to predict the biological process that the protein is involved in.
Here, we develop a probabilistic approach for protein function prediction using
network data, such as protein-protein interaction measurements. We take a
Bayesian approach to an existing Markov Random Field method by performing
simultaneous estimation of the model parameters and prediction of protein
functions. We use an adaptive Markov Chain Monte Carlo algorithm that leads to
more accurate parameter estimates and consequently to improved prediction
performance compared to the standard Markov Random Fields method. We tested our
method using a high quality S.cereviciae validation network
with 1622 proteins against 90 Gene Ontology terms of different levels of
abstraction. Compared to three other protein function prediction methods, our
approach shows very good prediction performance. Our method can be directly
applied to protein-protein interaction or coexpression networks, but also can be
extended to use multiple data sources. We apply our method to physical protein
interaction data from S. cerevisiae and provide novel
predictions, using 340 Gene Ontology terms, for 1170 unannotated proteins and we
evaluate the predictions using the available literature. 相似文献
107.
Cho YJ Choi JK Kim JH Lim YS Ham JS Kang DK Chun J Paik HD Kim GB 《Journal of bacteriology》2011,193(18):5021-5022
The draft genome sequence of Lactobacillus salivarius GJ-24 isolated from the feces of healthy adults was determined. Its properties, including milk fermentation activity and bacteriocin production, suggest its potential uses as a probiotic lactic acid bacterium and start culture for dairy products. 相似文献
108.
Lee JH Chae JP Lee JY Lim JS Kim GB Ham JS Chun J Kang DK 《Journal of bacteriology》2011,193(18):5030-5031
Lactobacillus johnsonii PF01, an autochthonous bacterium of the gastrointestinal tract, was isolated from a fecal sample from a piglet. The strain adhered specifically to the duodenal and jejunal epithelial cells of the piglet and had high bile resistance activity. Here we report the genomic sequence of L. johnsonii PF01. 相似文献
109.
110.
? In Cucumber mosaic virus (CMV) RNA replication, replicase-associated protein CMV 1a and RNA-dependent RNA polymerase protein CMV 2a are essential for formation of an active virus replicase complex on vacuolar membranes. ? To identify plant host factors involved in CMV replication, a yeast two-hybrid system was used with CMV 1a protein as bait. One of the candidate genes encoded Tsi1-interacting protein 1 (Tsip1), a zinc (Zn) finger protein. Tsip1 strongly interacted with CMV 2a protein, too. ? Formation of a Tsip1 complex involving CMV 1a or CMV 2a was confirmed in vitro and in planta. When 35S::Tsip1 tobacco (Nicotiana tabacum) plants were inoculated with CMV-Kor, disease symptom development was delayed and the accumulation of CMV RNAs and coat protein was decreased in both the infected local leaves and the uninfected upper leaves, compared with the wild type, whereas Tsip1-RNAi plants showed modestly but consistently increased CMV susceptibility. In a CMV replication assay, CMV RNA concentrations were reduced in the 35S::Tsip1 transgenic protoplasts compared with wild-type (WT) protoplasts. ? These results indicate that Tsip1 might directly control CMV multiplication in tobacco plants by formation of a complex with CMV 1a and CMV 2a. 相似文献