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11.
Máthé E Bates H Huikeshoven H Deák P Glover DM Cotterill S 《Developmental biology》2000,223(2):307-322
The Drosophila importin-alpha3 gene was isolated through its interaction with the large subunit of the DNA polymerase alpha in a two-hybrid screen. The predicted protein sequence of Importin-alpha3 is 65-66% identical to those of the human and mouse importin-alpha3 and alpha4 and 42.7% identical to that of Importin-alpha2 (Oho31/Pendulin), the previously reported Drosophila homologue. Both Importin-alpha3 and Importin-alpha2 interact with similar subsets of proteins in vitro, one of which is Ketel, the importin-beta homologue of Drosophila. importin-alpha3 is an essential gene, whose encoded protein is expressed throughout development. During early embryogenesis, Importin-alpha3 accumulates at the nuclear membrane of cleavage nuclei, whereas after blastoderm formation it is characteristically found within the interphase nuclei. Nuclear localisation is seen in several tissues throughout subsequent development. During oogenesis its concentration within the nurse cell nuclei increases during stages 7-10, concomitant with a decline in levels in the oocyte nucleus. Mutation of importin-alpha3 results in lethality throughout pupal development. Surviving females are sterile and show arrest of oogenesis at stages 7-10. Thus, Importin-alpha3-mediated nuclear transport is essential for completion of oogenesis and becomes limiting during pupal development. Since they have different expression patterns and subcellular localisation profiles, we suggest that the two importin-alpha homologues are not redundant in the context of normal Drosophila development. 相似文献
12.
Paulo FP Pimenta Alessandra S Orfano Ana C Bahia Ana PM Duarte Claudia M Ríos-Velásquez Fabrício F Melo Felipe AC Pessoa Giselle A Oliveira Keillen MM Campos Luis Martínez Villegas Nilton Barnabé Rodrigues Rafael Nacif-Pimenta Rejane C Sim?es Wuelton M Monteiro Rogerio Amino Yara M Traub-Cseko José BP Lima Maria GV Barbosa Marcus VG Lacerda Wanderli P Tadei Nágila FC Secundino 《Memórias do Instituto Oswaldo Cruz》2015,110(1):23-47
In the Americas, areas with a high risk of malaria transmission are mainly located in
the Amazon Forest, which extends across nine countries. One keystone step to
understanding the Plasmodium life cycle in Anopheles species from the Amazon Region
is to obtain experimentally infected mosquito vectors. Several attempts to colonise
Ano- pheles species have been conducted, but with only short-lived success or no
success at all. In this review, we review the literature on malaria transmission from
the perspective of its Amazon vectors. Currently, it is possible to develop
experimental Plasmodium vivax infection of the colonised and field-captured vectors
in laboratories located close to Amazonian endemic areas. We are also reviewing
studies related to the immune response to P. vivax infection of Anopheles aquasalis,
a coastal mosquito species. Finally, we discuss the importance of the modulation of
Plasmodium infection by the vector microbiota and also consider the anopheline
genomes. The establishment of experimental mosquito infections with Plasmodium
falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide
interesting models for studying malaria in the Amazonian scenario is important.
Understanding the molecular mechanisms involved in the development of the parasites
in New World vectors is crucial in order to better determine the interaction process
and vectorial competence. 相似文献
13.
White GE Cotterill A Addley MR Soilleux EJ Greaves DR 《Journal of molecular histology》2011,42(2):137-151
Treatment of cells with cytokines and growth factors leads to the synthesis of Suppressor of Cytokine Signalling (SOCS) proteins
that act as potent negative regulators of signalling via the Jak/STAT pathway. We used immunohistochemistry to identify cells
and pathologies where SOCS3 expression might influence acute and chronic inflammatory responses in human tissues. Epitope
and GFP tagged SOCS3 fusion proteins were localised predominantly in the nucleus of transfected cells and a validated anti
SOCS3 antiserum revealed the expression of SOCS3 in the nucleus and cytoplasm of macrophages, endothelial and epithelial cells
in a wide range of normal tissues in tissue microarrays (n = 31 different tissues). Nuclear SOCS3 was only seen in cells expressing a high level of the protein. Comparative immunostaining
of acute, chronically and granulomatously inflamed human tissues revealed higher levels of nuclear and cytoplasmic SOCS3 expression
in inflamed than in corresponding normal tissues, particularly in recruited leukocyte populations, but also in epithelia.
The staining appeared more intense, suggesting higher expression levels, in areas where inflammation was more acute, consistent
with the time course of SOCS3 induction described in vitro. Expression of SOCS3 protein by leucocytes and other cell types
in tissue sections could be a useful marker of cells undergoing acute or chronic stimulation by cytokines in vivo. 相似文献
14.
Julia Schwarzer Ernst Roelof Swartz Emmanuel Vreven Jos Snoeks Fenton Peter David Cotterill Bernhard Misof Ulrich Kurt Schliewen 《Proceedings. Biological sciences / The Royal Society》2012,279(1746):4389-4398
The megadiverse haplochromine cichlid radiations of the East African lakes, famous examples of explosive speciation and adaptive radiation, are according to recent studies, introgressed by different riverine lineages. This study is based on the first comprehensive mitochondrial and nuclear DNA dataset from extensive sampling of riverine haplochromine cichlids. It includes species from the lower River Congo and Angolan (River Kwanza) drainages. Reconstruction of phylogenetic hypotheses revealed the paradox of clearly discordant phylogenetic signals. Closely related mtDNA haplotypes are distributed thousands of kilometres apart and across major African watersheds, whereas some neighbouring species carry drastically divergent mtDNA haplotypes. At shallow and deep phylogenetic layers, strong signals of hybridization are attributed to the complex Late Miocene/Early Pliocene palaeohistory of African rivers. Hybridization of multiple lineages across changing watersheds shaped each of the major haplochromine radiations in lakes Tanganyika, Victoria, Malawi and the Kalahari Palaeolakes, as well as a miniature species flock in the Congo basin (River Fwa). On the basis of our results, introgression occurred not only on a spatially restricted scale, but massively over almost the whole range of the haplochromine distribution. This provides an alternative view on the origin and exceptional high diversity of this enigmatic vertebrate group. 相似文献
15.
Background
The human TTC4 protein is a TPR (tetratricopeptide repeat) motif-containing protein. The gene was originally identified as being localized in a genomic region linked to breast cancer and subsequent studies on melanoma cell lines revealed point mutations in the TTC4 protein that may be associated with the progression of malignant melanoma.Methodology/Principle Findings
Here we show that TTC4 is a nucleoplasmic protein which interacts with HSP90 and HSP70, and also with the replication protein CDC6. It has significant structural and functional similarities with a previously characterised Drosophila protein Dpit47. We show that TTC4 protein levels are raised in malignant melanoma cell lines compared to melanocytes. We also see increased TTC4 expression in a variety of tumour lines derived from other tissues. In addition we show that TTC4 proteins bearing some of the mutations previously identified from patient samples lose their interaction with the CDC6 protein.Conclusions/Significance
Based on these results and our previous work with the Drosophila Dpit47 protein we suggest that TTC4 is an HSP90 co-chaperone protein which forms a link between HSP90 chaperone activity and DNA replication. We further suggest that the loss of the interaction with CDC6 or with additional client proteins could provide one route through which TTC4 could influence malignant development of cells. 相似文献16.
Cotterill IC Rich JO Scholten MD Mozhaeva L Michels PC 《Biotechnology and bioengineering》2008,101(3):435-440
An efficient three-step, chemoenzymatic synthesis of unprotected doxorubicin-14-O-esters from doxorubicin hydrochloride salt is described. The key step is a lipase-catalyzed regioselective transesterification/esterification using commercially available acyl donors and doxorubicin reversibly derivatized with N-alloc to improve substrate loadings. The overall yield is ca. 60% and chromatographic purification is not required, thereby making the process more amenable to scale-up. 相似文献
17.
Dated Plant Phylogenies Resolve Neogene Climate and Landscape Evolution in the Cape Floristic Region
In the context of molecularly-dated phylogenies, inferences informed by ancestral habitat reconstruction can yield valuable insights into the origins of biomes, palaeoenvironments and landforms. In this paper, we use dated phylogenies of 12 plant clades from the Cape Floristic Region (CFR) in southern Africa to test hypotheses of Neogene climatic and geomorphic evolution. Our combined dataset for the CFR strengthens and refines previous palaeoenvironmental reconstructions based on a sparse, mostly offshore fossil record. Our reconstructions show remarkable consistency across all 12 clades with regard to both the types of environments identified as ancestral, and the timing of shifts to alternative conditions. They reveal that Early Miocene land surfaces of the CFR were wetter than at present and were dominated by quartzitic substrata. These conditions continue to characterize the higher-elevation settings of the Cape Fold Belt, where they have fostered the persistence of ancient fynbos lineages. The Middle Miocene (13–17 Ma) saw the development of perennial to weakly-seasonal arid conditions, with the strongly seasonal rainfall regime of the west coast arising ~6.5–8 Ma. Although the Late Miocene may have seen some exposure of the underlying shale substrata, the present-day substrate diversity of the CFR lowlands was shaped by Pliocene-Pleistocene events. Particularly important was renewed erosion, following the post-African II uplift episode, and the reworking of sediments on the coastal platform as a consequence of marine transgressions and tectonic uplift. These changes facilitated adaptive radiations in some, but not all, lineages studied. 相似文献
18.
Ohn Nyunt Joyce Y Wu Ivan N McGown Mark Harris Tony Huynh Gary M Leong David M Cowley Andrew M Cotterill 《The Clinical biochemist. Reviews / Australian Association of Clinical Biochemists》2009,30(2):67-74
Maturity Onset Diabetes of Young (MODY) is a monogenic and autosomal dominant form of diabetes mellitus with onset of the disease often before 25 years of age. It is due to dysfunction of pancreatic ß cells characterised by non-ketotic diabetes and absence of pancreatic auto-antibodies. It is frequently mistaken for type 1 or type 2 diabetes mellitus. Diagnosis of MODY is important as the GCK subtype has better prognosis and may not require any treatment. Subtypes HNF1A and HNF4A are sensitive to sulfonylureas, however diabetes complications are common if not treated early. Moreover, there is genetic implication for the patient and family. Rare MODY subtypes can be associated with pancreatic and renal anomalies as well as exocrine dysfunction of the pancreas. So far there are six widely accepted subtypes of MODY described but the list has grown to nine. Although the majority of diabetes mellitus in youth remains type 1 and the incidence of type 2 is rising, MODY should be considered in patients with non-ketotic diabetes at presentation, and in patients with a strong family history of diabetes mellitus without pancreatic auto-antibodies. Furthermore the diagnosis must be confirmed by molecular studies. With advancement in genomic technology, rapid screening for MODY mutations will become readily available in the future. 相似文献
19.
Karl A. Didier David Wilkie Iain Douglas-Hamilton Laurence Frank Nicholas Georgiadis Max Graham Festus Ihwagi Anthony King Alayne Cotterill Dan Rubenstein Rosie Woodroffe 《Biodiversity and Conservation》2009,18(7):1979-2000
Conservation projects may be reluctant to attempt Systematic Conservation Planning because existing methods are often prohibitive
in the time, money, data, and expertise they require. We tried to develop a “resource light” method for Systematic Conservation
Planning and applied it to the Ewaso Ngiro Landscape of central Kenya. Over a 6-month preparation period and 1-week participatory
workshop, we used expert assessments to select focal biodiversity features, set quantitative targets for these, map their
current distribution, vulnerability, potential for recovery, and conservation costs, and, finally, map cross-feature conservation
priorities. Preparation for and facilitation of the workshop required time investment by one part-time workshop coordinator,
eight workshop committee members, six ecosystem experts, and two GIS technicians. Total time investment was approximately
56.5 person-weeks spread over facilitators and 40 workshop participants. Monetary costs for the workshop were approximately
$US 42,000, excluding investments made by researchers previous to this project. Costs for a similar workshop could vary substantially,
depending on need to cover salaries, international travel, food and lodging, and the number of participants. To stay within
our resource constraints, we completed the exercise for only four of nine focal biodiversity features and did not negotiate
trade-offs between conservation and human land-uses or use planning software to identify “optimal networks” of conservation
areas. These were not considered critical for conservationists to try Systematic Conservation Planning, introduce landscape-scale
conservation concepts to stakeholders, and begin implementing landscape conservation strategies. Participants agreed that
further work would be needed to complete and update the planning process. Due to the lack of comparative cost data from similar
planning exercises, we cannot definitively conclude that our approach was “resource light”, although we suspect it is within
the constraints of most site-based conservation projects. 相似文献
20.
Chen Chun Pai Ignacio García Shao Win Wang Sue Cotterill Stuart A. MacNeill Stephen E. Kearsey 《Molecular biology of the cell》2009,20(4):1213-1222
The tetrameric GINS complex, consisting of Sld5-Psf1-Psf2-Psf3, plays an essential role in the initiation and elongation steps of eukaryotic DNA replication, although its biochemical function is unclear. Here we investigate the function of GINS in fission yeast, using fusion of Psf1 and Psf2 subunits to a steroid hormone-binding domain (HBD) to make GINS function conditional on the presence of β-estradiol. We show that inactivation of Psf1-HBD causes a tight but rapidly reversible DNA replication arrest phenotype. Inactivation of Psf2-HBD similarly blocks premeiotic DNA replication and leads to loss of nuclear localization of another GINS subunit, Psf3. Inactivation of GINS has distinct effects on the replication origin association and chromatin binding of two of the replicative DNA polymerases. Inactivation of Psf1 leads to loss of chromatin binding of DNA polymerase ε, and Cdc45 is similarly affected. In contrast, chromatin association of the catalytic subunit of DNA polymerase α is not affected by defective GINS function. We suggest that GINS functions in a pathway that involves Cdc45 and is necessary for DNA polymerase ε chromatin binding, but that a separate pathway sets up the chromatin association of DNA polymerase α. 相似文献