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71.
Tanya Marchant Ritgak Dimka Tilley-Gyado Tsegahun Tessema Kultar Singh Meenakshi Gautham Nasir Umar Della Berhanu Simon Cousens Joanna RM Armstrong Schellenberg 《PloS one》2015,10(5)
BackgroundFamilies in high mortality settings need regular contact with high quality services, but existing population-based measurements of contacts do not reflect quality. To address this, in 2012, we designed linked household and frontline worker surveys for Gombe State, Nigeria, Ethiopia, and Uttar Pradesh, India. Using reported frequency and content of contacts, we present a method for estimating the population level coverage of high quality contacts.ConclusionsMeasuring content of care to reflect the quality of contacts can reveal missed opportunities to deliver best possible health care. 相似文献
72.
Carl A. St. John Thaddaeus J. Buser Victoria E. Kee Sergei Kirilchik Bakhtiar Bogdanov David Neely Michael Sandel Andres Aguilar 《Molecular ecology》2022,31(1):238-251
Insights into the generation of diversity in both plants and animals have relied heavily on studying speciation in adaptive radiations. Russia's Lake Baikal has facilitated a putative adaptive radiation of cottid fishes (sculpins), some of which are highly specialized to inhabit novel niches created by the lake's unique geology and ecology. Here, we test evolutionary relationships and novel morphological adaptation in a piece of this radiation: the Baikal cottid genus, Cottocomephorus, a morphologically derived benthopelagic genus of three described species. We used a combination of mitochondrial DNA and restriction site associated DNA sequencing from all Cottocomephorus species. Analysis of mitochondrial cytochrome b haplotypes was only able to two resolve two lineages: C. grewingkii and C. comephoroides/inermis. Phylogenetic inference, principal component analysis, and faststructure of genome-wide SNPs uncovered three lineages within Cottocomephorus: C. comephoroides, C. inermis and C. grewingkii. We found recent divergence and admixture between C. comephoroides and C. inermis and deep divergence between these two species and C. grewingkii. Contrasting other fish radiations, we found no evidence of ancient hybridization among Cottocomephorus species. Digital morphology revealed highly derived pelagic phenotypes that reflect divergence by specialization to the benthopelagic niche in Cottocomephorus. Among Cottocomephorus species, we found evidence of ongoing adaptation to the pelagic zone. This pattern highlights the importance of speciation along a benthic-pelagic gradient seen in Cottocomephorus and across other adaptive fish radiations. 相似文献
73.
74.
75.
Reduced natural selection associated with low recombination in Drosophila melanogaster 总被引:8,自引:1,他引:7
Synonymous codons are not used equally in many organisms, and the extent of
codon bias varies among loci. Earlier studies have suggested that more
highly expressed loci in Drosophila melanogaster are more biased,
consistent with findings from several prokaryotes and unicellular
eukaryotes that codon bias is partly due to natural selection for
translational efficiency. We link this model of varying selection intensity
to the population-genetics prediction that the effectiveness of natural
selection is decreased under reduced recombination. In analyses of 385 D.
melanogaster loci, we find that codon bias is reduced in regions of low
recombination (i.e., near centromeres and telomeres and on the fourth
chromosome). The effect does not appear to be a linear function of
recombination rate; rather, it seems limited to regions with the very
lowest levels of recombination. The large majority of the genome apparently
experiences recombination at a sufficiently high rate for effective natural
selection against suboptimal codons. These findings support models of the
Hill-Robertson effect and genetic hitchhiking and are largely consistent
with multiple reports of low levels of DNA sequence variation in regions of
low recombination.
相似文献
76.
Kappa-chain constant-region gene sequences in genus Rattus: coding regions are diverging more rapidly than noncoding regions 总被引:2,自引:0,他引:2
We have determined the nucleotide sequence of a 1,200-base pair (bp)
genomic fragment that includes the kappa-chain constant-region gene (C
kappa) from two species of native Australian rodents, Rattus leucopus
cooktownensis and Rattus colletti. Comparison of these sequences with each
other and with other rodent C kappa genes shows three surprising features.
First, the coding regions are diverging at a rate severalfold higher than
that of the nearby noncoding regions. Second, replacement changes within
the coding region are accumulating at a rate at least as great as that of
silent changes. Third, most of the amino acid replacements are localized in
one region of the C kappa domain--namely, the carboxy-terminal "bends" in
the alpha-carbon backbone. These three features have previously been
described from comparisons of the two allelic forms of C kappa genes in R.
norvegicus. These data imply the existence of considerable evolutionary
constraints on the noncoding regions (based on as yet undetermined
functions) or powerful positive selection to diversify a portion of the
constant-region domain (whose physiological significance is not known).
These surprising features of C kappa evolution appear to be characteristic
only of closely related C kappa genes, since comparison of rodent with
human sequences shows the expected greater conservation of coding regions,
as well as a predominance of silent nucleotide substitutions within the
coding regions.
相似文献
77.
Cox CD Breslin MJ Mariano BJ Coleman PJ Buser CA Walsh ES Hamilton K Huber HE Kohl NE Torrent M Yan Y Kuo LC Hartman GD 《Bioorganic & medicinal chemistry letters》2005,15(8):2041-2045
Optimization of high-throughput screening (HTS) hits resulted in the discovery of 3,5-diaryl-4,5-dihydropyrazoles as potent and selective inhibitors of KSP. Dihydropyrazole 15 is a potent, cell-active KSP inhibitor that induces apoptosis and generates aberrant mitotic spindles in human ovarian carcinoma cells at low nanomolar concentrations. X-ray crystallographic evidence is presented which demonstrates that these inhibitors bind in an allosteric pocket of KSP distant from the nucleotide and microtubule binding sites. 相似文献
78.
Becca Asquith Angelina J Mosley Adrian Heaps Yuetsu Tanaka Graham P Taylor Angela R McLean Charles RM Bangham 《Retrovirology》2005,2(1):1-9
Background
Cellular infection with human immunodeficiency virus (HIV) both in vitro and in vivo requires a member of the chemokine receptor family to act as a co-receptor for viral entry. However, it is presently unclear to what extent the interaction of HIV proteins with chemokine receptors generates intracellular signals that are important for productive infection.Results
In this study we have used a recently described family of chemokine inhibitors, termed BSCIs, which specifically block chemokine-induced chemotaxis without affecting chemokine ligands binding to their receptors. The BSCI termed Peptide 3 strongly inhibited CCR5 mediated HIV infection of THP-1 cells (83 ± 7% inhibition assayed by immunofluoresence staining), but had no effect on gp120 binding to CCR5. Peptide 3 did not affect CXCR4-dependent infection of Jurkat T cells.Conclusion
These observations suggest that, in some cases, intracellular signals generated by the chemokine coreceptor may be required for a productive HIV infection. 相似文献79.
Andreas Holbro Helen Baldomero Francesco Lanza Christian Chabannon John A. Snowden Andreas Buser Laura Infanti Nina Worel Anna Sureda Manuela Badoglio Jakob Passweg Chiara Bonini 《Cytotherapy》2018,20(3):453-460
Background
There is considerable heterogeneity in processing of stem cells for hematopoietic stem cell transplantation across Europe. The Foundation for the Accreditation of Cellular Therapy (FACT)–Joint Accreditation Committee International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation (EBMT) (JACIE) standards provide minimum guidelines that, however, leave room for significant variations in practices at the individual transplantation center (TC).Methods
To better understand the extent of heterogeneity in storage conditions, quality controls (QCs), graft processing and disposal, a questionnaire was developed, reviewed by the Cellular Therapy and Immunobiology Working Party (CTIWP) and sent to all EBMT TCs.Results
In this study, 288 TCs from 46 countries (32 European, 14 associated) responded to the survey. Long-term storage is performed mainly either in liquid nitrogen or in the vapor phase of liquid nitrogen with 10% dimethyl sulfoxide (DMSO; 58% of centers). In case of microbiological contamination, most TCs make a case-by-case decision in collaboration with the clinicians. CD34+ counts are performed routinely either before and/or after thawing. Some centers perform additional QCs. DMSO is generally not removed (83%) and the graft is thawed at the bedside (68%) in a water bath (78%). There is heterogeneity between the centers regarding duration of storage and graft disposal.Discussion
Overall, this survey demonstrates that the majority of responding TCs uses standardized procedures (intracenter standardization). However, significant intercenter variations persist, which warrant further standardization and investigations on clinical and financial consequences. Additionally, efforts should be undertaken to provide more specific international guidelines on storage duration and graft disposal, which may also have an important impact on health care services worldwide. 相似文献80.
H Langen T Epprecht M Linden T Hehlgans B Gutte H R Buser 《European journal of biochemistry》1989,182(3):727-735
Heme compounds, in combination with a reducing agent and oxygen, can express various activities of cytochrome P-450 enzymes. In the present study it was found that a mixture of hemin and excess cysteine was able to degrade the insecticide DDT partially. The major products were three water-soluble, non-toxic conjugates of DDT metabolites with cysteine which had lost two or three of the five chlorine atoms of DDT per molecule and whose structures were elucidated by gas chromatography/mass spectrometry. In 0.05 M NH4HCO3, pH 7.7/ethanol (5:6, by vol.), the degradation reaction catalyzed by the hemin-cysteine model system was at least 8 x 10(4) times faster than the uncatalyzed reaction. In the presence of a designed 24-residues polypeptide or beta-casein, two DDT-binding proteins, an additional fourfold increase in the rate of DDT degradation was observed. Although the concentrations of DDT and cysteine occurring in an organism would be expected to be lower than those in the experiments described, the formation of water-soluble conjugates of DDT metabolites with cysteine (and other amino acids) could also play a role in metabolism and excretion of DDT in vivo. 相似文献