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31.
Despite recent advances in blood safety by careful donor selection and implementation of infectious disease testing, transmission of viruses, bacteria and parasites by transfusion can still rarely occur. One approach to reduce the residual risk from currently tested pathogens and to protect against the emergence of new ones is to investigate methods for pathogen inactivation. The use of photosensitizing dyes for pathogen inactivation has been studied in both red cell and platelet blood components. Optimal properties of sensitizing dyes for use in red cell suspensions include selection of dyes that traverse cell and viral membranes, bind to nucleic acids, absorb light in the red region of the spectrum, inactivate a wide range of pathogens, produce little red cell photodamage from dye not bound to nucleic acid and do not hemolyze red cells in the dark. Early research at the American Red Cross focused on the use of a class of dyes with rigid structures, such as the phenothiazine dyes, beginning with the prototypical sensitizer methylene blue. Results revealed that methylene blue phototreatment could inactivate extracellular virus, but resulted in undesirable defects in the red cell membrane that resulted in enhanced hemolysis that became evident during extended refrigerated blood storage. In addition, methylene blue phototreatment could neither inactivate intracellular viruses nor appreciably inactivate bacteria under conditions of extracellualar viral killing. Attempts to improve intracellular viral inactivation led to the investigations of more hydrophobic phenothiazines, such as methylene violet or dimethylmethylene blue. Although these dyes could inactivate intracellular virus, problems with increased red cell membrane damage and hemolysis persisted or increased. Further studies using red cell additive storage solutions containing high levels of the impermeable ion, citrate, to protect against colloidal osmotic hemolysis as well as competitive inhibitors to limit sensitizer binding to red cell membranes revealed that photoinduced hemolysis stemmed from dye bound to the red cell membrane as well as dye free in solution. Use of red cell additive solutions to prevent colloidal-osmotic hemolysis and use of novel flexible dyes that only act as sensitizers when bound to their targets are two techniques that currently are under investigation for reducing red cell damage. Ultimately, the decision to implement a photodynamic method for pathogen reduction will be determined by weighing the risks of unintended adverse consequences of the procedure itself, such as the potential for genotoxicity and allergic reactions, against the cost and benefits of its implementation. 相似文献
32.
33.
A molecular and evolutionary study of the beta-globin gene family of the Australian marsupial Sminthopsis crassicaudata 总被引:1,自引:0,他引:1
Cooper SJ; Murphy R; Dolman G; Hussey D; Hope RM 《Molecular biology and evolution》1996,13(7):1012-1022
Beta-globin gene families in eutherians (placental mammals) consist of a
set of four or more developmentally regulated genes which are closely
linked and, in general, arranged in the order 5'-embryonic/fetal genes-
adult genes-3'. This cluster of genes is proposed to have arisen by tandem
duplication of ancestral beta-globin genes, with the first duplication
occurring 200 to 155 MYBP just prior to a period in mammalian evolution
when eutherians and marsupials diverged from a common ancestor. In this
paper we trace the evolutionary history of the beta-globin gene family back
to the origins of these mammals by molecular characterization of the
beta-globin gene family of the Australian marsupial Sminthopsis
crassicaudata. Using Southern and restriction analysis of total genomic DNA
and bacteriophage clones of beta-like globin genes, we provide evidence
that just two functional beta-like globin genes exist in this marsupial,
including one embryonic- expressed gene (S.c-epsilon) and one
adult-expressed gene (S.c-beta), linked in the order 5'-epsilon-beta-3'.
The entire DNA sequence of the adult beta-globin gene is reported and shown
to be orthologous to the adult beta-globin genes of the North American
marsupial Didelphis virginiana and eutherian mammals. These results,
together with results from a phylogenetic analysis of mammalian beta-like
globin genes, confirm the hypothesis that a two-gene cluster, containing an
embryonic- and an adult-expressed beta-like globin gene, existed in the
most recent common ancester of marsupials and eutherians. Northern analysis
of total RNA isolated from embryos and neonatals indicates that a switch
from embryonic to adult gene expression occurs at the time of birth,
coinciding with the transfer of the marsupial from a uterus to a pouch
environment.
相似文献
34.
Paul R McAdam Charles W Vander Broek Diane SJ Lindsay Melissa J Ward Mary F Hanson Michael Gillies Mick Watson Joanne M Stevens Giles F Edwards J Ross Fitzgerald 《Genome biology》2014,15(11)
Background
Legionnaires’ disease is a severe form of pneumonia caused by the environmental bacterium Legionella pneumophila. Outbreaks commonly affect people with known risk factors, but the genetic and pathogenic complexity of L. pneumophila within an outbreak is not well understood. Here, we investigate the etiology of the major Legionnaires’ disease outbreak that occurred in Edinburgh, UK, in 2012, by examining the evolutionary history, genome content, and virulence of L. pneumophila clinical isolates.Results
Our high resolution genomic approach reveals that the outbreak was caused by multiple genetic subtypes of L. pneumophila, the majority of which had diversified from a single progenitor through mutation, recombination, and horizontal gene transfer within an environmental reservoir prior to release. In addition, we discover that some patients were infected with multiple L. pneumophila subtypes, a finding which can affect the certainty of source attribution. Importantly, variation in the complement of type IV secretion systems encoded by different genetic subtypes correlates with virulence in a Galleria mellonella model of infection, revealing variation in pathogenic potential among the outbreak source population of L. pneumophila.Conclusions
Taken together, our study indicates previously cryptic levels of pathogen heterogeneity within a Legionnaires’ disease outbreak, a discovery that impacts on source attribution for future outbreak investigations. Furthermore, our data suggest that in addition to host immune status, pathogen diversity may be an important influence on the clinical outcome of individual outbreak infections.Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0504-1) contains supplementary material, which is available to authorized users. 相似文献35.
Greg J Poet Ojore BV Oka Marcel van Lith Zhenbo Cao Philip J Robinson Marie Anne Pringle Elias SJ Arnér Neil J Bulleid 《The EMBO journal》2017,36(5):693-702
Folding of proteins entering the secretory pathway in mammalian cells frequently requires the insertion of disulfide bonds. Disulfide insertion can result in covalent linkages found in the native structure as well as those that are not, so‐called non‐native disulfides. The pathways for disulfide formation are well characterized, but our understanding of how non‐native disulfides are reduced so that the correct or native disulfides can form is poor. Here, we use a novel assay to demonstrate that the reduction in non‐native disulfides requires NADPH as the ultimate electron donor, and a robust cytosolic thioredoxin system, driven by thioredoxin reductase 1 (TrxR1 or TXNRD1). Inhibition of this reductive pathway prevents the correct folding and secretion of proteins that are known to form non‐native disulfides during their folding. Hence, we have shown for the first time that mammalian cells have a pathway for transferring reducing equivalents from the cytosol to the ER, which is required to ensure correct disulfide formation in proteins entering the secretory pathway. 相似文献
36.
37.
The harbor seal (Phoca vitulina) has the most extensive distribution of any
phocid seal species. An analysis of population structure in this species
across its European range was made using 7 phocid derived microsatellites
in a sample of 1,029 individuals from 12 separate geographic areas. Despite
the species potential for long-distance movement, significant genetic
differentiation between areas was observed using an unbiased estimator of
RST. Six distinct population units were identified: Ireland-Scotland,
English east coast, Waddensea, western Scandinavia
(Norway-Kattegat-Skagerrak-west Baltic), east Baltic, and Iceland. Little
local substructuring is present along coastlines with a continuous
distribution of breeding animals, but differentiation does increase with
geographic distance. The degree of differentiation is greater over
equivalent distances where the distribution is discontinuous, such as along
coasts where breeding colonies are separated by large distances or by
stretches of open sea. Patterns of population differentiation derived from
microsatellites are very similar to those obtained from previous
mitochondrial DNA analysis and suggest that philopatry in harbor seals
operates over 300-500 km. In Europe, harbor seals have experienced a
complex demographic history and patterns of population structure are likely
to have been affected by natural environmental influences such as
Pleistocene glaciations and epizootics. Comparison of Nm values from an
unbiased estimator of RST, GST, and theta are consistent and, in some
cases, may indicate populations where conditions deviate from the
expectations of the RST model.
相似文献
38.
Genes essential for the production of a linear, bacterial (1-->3)-beta-
glucan, curdlan, have been cloned for the first time from Agrobacterium sp.
ATCC31749. The genes occurred in two, nonoverlapping, genomic fragments
that complemented different sets of curdlan( crd )-deficient
transposon-insertion mutations. These were detected as colonies that failed
to stain with aniline blue, a (1-->3)-beta-glucan specific dye. One
fragment carried a biosynthetic gene cluster (locus I) containing the
putative curdlan synthase gene, crdS, and at least two other crd genes. The
second fragment may contain only a single crd gene (locus II).
Determination of the DNA sequence adjacent to several locus I mutations
revealed homology to known sequences only in the cases of crdS mutations.
Complete sequencing of the 1623 bp crdS gene revealed highest similarities
between the predicted CrdS protein (540 amino acids) and glycosyl
transferases with repetitive action patterns. These include bacterial
cellulose synthases (and their homologs), which form
(1-->4)-beta-glucans. No similarity was detected with putative
(1-->3)- beta-glucan synthases from yeasts and filamentous fungi.
Whatever the determinants of the linkage specificity of these beta-glucan
synthases might be, these results raise the possibility that
(1-->3)-beta-glucans and (1-->4)-beta-glucans are formed by related
catalytic polypeptides.
相似文献
39.
An opercular tag for marking adult milkfish ( Chanos chanos Forsskal) and seabass ( Lates calcarifer Bloch) is described. High tag retention and relatively low mortality rates were observed in adult fish handled two to ten times during 14-to 60-day tests. The features and advantages of the tag for marking large-sized fish in short-term studies are discussed.
Eine preiswerte Markierung für Kurzzeitstudien des Milchfisches (Chanos chanos Forsskal) und der Centropomidae (Lates calcarifer Bloch)
Eine Kiemendeckel-Markierung für adulte Milchfische (Chanos chanos Forsskal) und Centropomidae (Lates calcacifer Bloch) wird beschrieben. Sie zeichnet sich durch gute Haltbarkeit aus und verursacht relativ geringe Mortalität bei adulten Fischen, die in Versuchen von 14 bis 60 Tage Dauer 2-bis 10mal untersucht wurden. Die Eigenschaften und Vorteile dieser Markierung für große Fische in Kurzzeitstudien werden diskutiert.
Un marquage économique pour des études de courte durée du chanidé (Chanos chanos Forsskal) et du centropomidé (Lates calcarifer Bloch)
Un marquage d'opercule pour les chanidés (Chanos chanos Forsskal) et les centropomidés (Lates calcarifer Bloch) adultes est décrit. Une bonne conservation et une mortalité relativement basse ont été observées chez des poissons adultes examinés 2 à 10 fois pendant des expériences d'une durée de 14 à 60 jours. Les caractéristiques et les avantages du marquage de poissons de grande taille pendant des expériences d'une courte durée sont discutés. 相似文献
Zusammenfassung
Eine preiswerte Markierung für Kurzzeitstudien des Milchfisches (Chanos chanos Forsskal) und der Centropomidae (Lates calcarifer Bloch)
Eine Kiemendeckel-Markierung für adulte Milchfische (Chanos chanos Forsskal) und Centropomidae (Lates calcacifer Bloch) wird beschrieben. Sie zeichnet sich durch gute Haltbarkeit aus und verursacht relativ geringe Mortalität bei adulten Fischen, die in Versuchen von 14 bis 60 Tage Dauer 2-bis 10mal untersucht wurden. Die Eigenschaften und Vorteile dieser Markierung für große Fische in Kurzzeitstudien werden diskutiert.
Résumé
Un marquage économique pour des études de courte durée du chanidé (Chanos chanos Forsskal) et du centropomidé (Lates calcarifer Bloch)
Un marquage d'opercule pour les chanidés (Chanos chanos Forsskal) et les centropomidés (Lates calcarifer Bloch) adultes est décrit. Une bonne conservation et une mortalité relativement basse ont été observées chez des poissons adultes examinés 2 à 10 fois pendant des expériences d'une durée de 14 à 60 jours. Les caractéristiques et les avantages du marquage de poissons de grande taille pendant des expériences d'une courte durée sont discutés. 相似文献
40.
To determine the salivary secretory immunoglobulin A (sIgA) response to repeated bouts of unaccustomed, downhill running (eccentrically biased) and examine potential protective immunological adaption from a repeated bout effect. Eleven active but untrained males (age: 19.7±0.4 years; VO2peak: 47.8± 3.6 ml · kg−1 · min −1) performed two 60 min bouts (Run 1 and Run 2) of downhill running (−13.5% gradient), separated by 14 days, at a speed eliciting 75% of their VO2peak on a level grade. Saliva samples were collected before (baseline), immediately post exercise (IPE), and every hour for 12 h and every 24 h for 6 days after each run. Salivary sIgA concentration was measured and sIgA secretion rate was calculated. Results were analysed using repeated measures ANOVA (12 h period: 2x14; 24 h intervals: 2x7; p ≤ 0.05) with Tukey post-hoc tests where appropriate. Results are reported as means ± SE. There was a significant (p < 0.0001) interaction effect for sIgA secretion rate, IPE, with higher values after Run 2, as well as a significant (p < 0.01) time effect with elevated levels IPE and between 24 h and 144 h. There was a run effect (p < 0.0001), with the sIgA secretion rate significantly higher after Run 2. Repeated bouts of unaccustomed, eccentrically biased exercise induced alterations in the salivary sIgA secretion rate. This may serve as a protective mucosal adaptation to exercise-induced tissue damage. 相似文献