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121.
Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes 总被引:6,自引:0,他引:6
Yeoh S O'Donnell RA Koussis K Dluzewski AR Ansell KH Osborne SA Hackett F Withers-Martinez C Mitchell GH Bannister LH Bryans JS Kettleborough CA Blackman MJ 《Cell》2007,131(6):1072-1083
The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte. 相似文献
122.
Lee M. Yeoh Christopher D. Goodman Nathan E. Hall Giel G. van?Dooren Geoffrey I. McFadden Stuart A. Ralph 《Nucleic acids research》2015,43(9):4661-4675
Single genes are often subject to alternative splicing, which generates alternative mature mRNAs. This phenomenon is widespread in animals, and observed in over 90% of human genes. Recent data suggest it may also be common in Apicomplexa. These parasites have small genomes, and economy of DNA is evolutionarily favoured in this phylum. We investigated the mechanism of alternative splicing in Toxoplasma gondii, and have identified and localized TgSR3, a homologue of ASF/SF2 (alternative-splicing factor/splicing factor 2, a serine-arginine–rich, or SR protein) to a subnuclear compartment. In addition, we conditionally overexpressed this protein, which was deleterious to growth. qRT-PCR was used to confirm perturbation of splicing in a known alternatively-spliced gene. We performed high-throughput RNA-seq to determine the extent of splicing modulated by this protein. Current RNA-seq algorithms are poorly suited to compact parasite genomes, and hence we complemented existing tools by writing a new program, GeneGuillotine, that addresses this deficiency by segregating overlapping reads into distinct genes. In order to identify the extent of alternative splicing, we released another program, JunctionJuror, that detects changes in intron junctions. Using this program, we identified about 2000 genes that were constitutively alternatively spliced in T. gondii. Overexpressing the splice regulator TgSR3 perturbed alternative splicing in over 1000 genes. 相似文献
123.
DNA fingerprinting was performed on 64 strains of Aspergillus oryzae and 1 strain of Aspergillus sojae isolated from soy sauce factories within Malaysia and Southeast Asia that use traditional methods in producing “tamari-type”
Cantonese soy sauce. PstI digests of total genomic DNA from each isolate were probed using the pAF28 repetitive sequence. Strains of A. oryzae were distributed among 32 genotypes (30 DNA fingerprint groups). Ten genotypes were recorded among 17 A. oryzae isolates from a single soy sauce factory. Genotypes Ao-46 and GTAo-47, represented by 8 and 5 strains, respectively, were
isolated from a soy sauce factory in Kuala Lumpur and factories in two Malaysian states. Four strains of GTAo-49, isolated
from three soy sauce factories in Malaysia; each produced sclerotia. Two strains were found to be naturally occurring color
mutants of NRRL 32623 (GTAo-49) and NRRL 32668 (GTAo-52). Only two fingerprint matches were produced with the 43 DNA fingerprint
groups in our database, representing A. oryzae genotypes from Japan, China, and Taiwan. Aspergillus sojae NRRL 32650 produced a fingerprint matching GTAo-9, the only known genotype representing koji strains of A. sojae. No aflatoxin was detected in broth cultures of these koji strains as determined by TLC. 相似文献
124.
Amplified fragment length polymorphism (AFLP) markers were used in the characterization of eight cassava varieties. This nonradioactive AFLP system was customized in terms of the choice of restriction enzymes used and the selection of nucleotides added to the 3' end of primers. EcoRI/MseI and HindIII/MseI fragments generally gave monomorphic profiles while ApaI/TaqI fragments produced polymorphic profiles suggesting a genome with high G + C content. It was possible to identify the eight cassava varieties used in this study using CTG as selective bases at the TaqI primer. For cassava, the AFLP system provided a higher number of loci detected per run when compared to RAPD. The reliability accompanying AFLP analysis would thus make it suitable for the characterization of cassava varieties. 相似文献
125.
Jing Wui Yeoh Sudhaghar S/O Jayaraman Sean Guo‐Dong Tan Premkumar Jayaraman Maciej B. Holowko Jingyun Zhang Chang‐Wei Kang Hwa Liang Leo Chueh Loo Poh 《Biotechnology and bioengineering》2021,118(1):305-318
Due to sustainability concerns, bio‐based production capitalizing on microbes as cell factories is in demand to synthesize valuable products. Nevertheless, the nonhomogenous variations of the extracellular environment in bioprocesses often challenge the biomass growth and the bioproduction yield. To enable a more rational bioprocess optimization, we have established a model‐driven approach that systematically integrates experiments with modeling, executed from flask to bioreactor scale, and using ferulic acid to vanillin bioconversion as a case study. The impacts of mass transfer and aeration on the biomass growth and bioproduction performances were examined using minimal small‐scale experiments. An integrated model coupling the cell factory kinetics with the three‐dimensional computational hydrodynamics of bioreactor was developed to better capture the spatiotemporal distributions of bioproduction. Full‐factorial predictions were then performed to identify the desired operating conditions. A bioconversion yield of 94% was achieved, which is one of the highest for recombinant Escherichia coli using ferulic acid as the precursor. 相似文献
126.
Katharine J. Goodall Megan L. Finch-Edmondson Joanne van Vuuren George C. Yeoh Ian E. Gentle James E. Vince Paul G. Ekert David L. Vaux Bernard A. Callus 《PloS one》2016,11(11)
Apoptosis mediated by Bax or Bak is usually thought to be triggered by BH3-only members of the Bcl-2 protein family. BH3-only proteins can directly bind to and activate Bax or Bak, or indirectly activate them by binding to anti-apoptotic Bcl-2 family members, thereby relieving their inhibition of Bax and Bak. Here we describe a third way of activation of Bax/Bak dependent apoptosis that does not require triggering by multiple BH3-only proteins. In factor dependent myeloid (FDM) cell lines, cycloheximide induced apoptosis by a Bax/Bak dependent mechanism, because Bax-/-Bak-/- lines were profoundly resistant, whereas FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Addition of cycloheximide led to the rapid loss of Mcl-1 but did not affect the expression of other Bcl-2 family proteins. In support of these findings, similar results were observed by treating FDM cells with the CDK inhibitor, roscovitine. Roscovitine reduced Mcl-1 abundance and caused Bax/Bak dependent cell death, yet FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Therefore Bax/Bak dependent apoptosis can be regulated by the abundance of anti-apoptotic Bcl-2 family members such as Mcl-1, independently of several known BH3-only proteins. 相似文献
127.
128.
129.
Oval cells observed in some experimental models of hepatocarcinogenesis can function as stem cells capable of differentiating
into hepatocytes and bile ductular cells. Using markers which characterise embryonic hepatocytes, we showed that oval cells
display different patterns of gene expression, suggesting some are more mature than others. In this study we looked for oval
cells in developing liver, predicting that they are abundant in embryonic liver and decline in number during development.
Albumin (ALB) serves as a liver-specific marker, and the isoenzymes of pyruvate kinase, M2-PK and L-PK, are used to identify immature and mature hepatocytes, respectively. Small oval-shaped cells expressing ALB,
M2-PK and L-PK are found near the vascular spaces and portal areas in 20-day gestation (E20), E21, newborn, 3-day and 1-week-old
rat liver. Similar cells expressing ALB and M2-PK, but not L-PK are seen only periportally in adult liver. These are abundant in early embryonic liver and decrease in number
during development until only a few, located periportally, persist in the adult. Oval cells, located periportally a few days
after commencing a choline-deficient, ethionine-supplemented diet, co-express ALB and M2-PK. Their similarity with respect to markers, morphology and location suggests that oval-shaped cells may be the progenitors
of oval cells.
Accepted: 18 October 1996 相似文献
130.
A series of potential UDP-sugar mimics were readily synthesised by copper(I) catalysed modified Huisgen cycloaddition of the corresponding α-propargyl glycosides with 5-azido uridine in aqueous solution. None of the compounds accessed displayed significant inhibitory activity at concentrations of up to 4.5 mM in an assay against bovine milk β-1,4-galactosyltransferase. 相似文献