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Timothy?M?CoxEmail author Dominick?Amato Carla?EM?Hollak Cecile?Luzy Mariabeth?Silkey Ruben?Giorgino Robert?D?Steiner for the Miglustat Maintenance Study Group 《Orphanet journal of rare diseases》2012,7(1):102
Background
Previous studies have provided equivocal data on the use of miglustat as maintenance therapy in Gaucher disease type 1. We report findings from a clinical trial evaluating the effects of miglustat treatment in patients with stable type 1 Gaucher disease after enzyme therapy.Methods
Adult type 1 Gaucher disease patients stabilized during at least 3 years of previous enzyme therapy were included in this 2-year, prospective, open-label non-inferiority study. The primary endpoint was percent change from baseline in liver volume. Secondary endpoints included changes in spleen volume, hemoglobin concentration and platelet count.Results
Forty-two patients were enrolled (mean±SD age, 45.1±12.7 years; previous enzyme therapy duration 9.5±4.0 years). Median (range) exposure to miglustat 100 mg t.i.d. was 658 (3–765) days. Twenty-one patients discontinued treatment prematurely; 13 due to adverse events, principally gastrointestinal. The upper 95% confidence limit of mean percent change in liver volume from baseline to end of treatment was below the non-inferiority margin of 10% (–1.1%; 95%CI ?6.0, 3.9%). Mean (95%CI) changes in spleen volume, hemoglobin concentration and platelet count were 102 (24,180) mL, –0.95 (?1.38, –0.53) g/dL and ?44.1 (–57.6, –30.7) ×109/L, respectively.Conclusions
The primary efficacy endpoint was met; overall there was no change in liver volume during 24 months of miglustat therapy. Several patients showed a gradual deterioration in some disease manifestations, suggesting that miglustat could maintain clinical stability, but not in all patients. Miglustat demonstrated a predictable profile of safety and tolerability that was consistent with that reported in previous clinical trials and experience in clinical practice.Trial registration
Clinicaltrials.gov identifier NCT0031904674.
Here we study the properties of cell hybrids produced by the fusion of embryonal stem cells and differentiated ones. During in vitrocultivation, such hybrids predominantly lose the somatic partner chromosomes, although the loss of the embryonic partner autosomes is also common in the clones; i.e., this is a bidirectional process. The use of a selective media allows the isolation of the clones, with the embryonal X chromosome replaced by the somatic genome homolog. The cell hybrids with a near-diploid chromosome set preserve the high-level pluripotency properties of the embryonal partner including the capacity to form chimeras after their introduction in the blastocoel. An investigation of the chimeric animals demonstrated a reprogramming of the somatic X chromosome in the course of development. The prospective identification of the chromosomes involved in the maintenance of pluripotency and studies of its cis-and trans-regulation in the cell hybrid genome are discussed. 相似文献
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Bubenshchikova E Kaftanovskaya E Motosugi N Fujimoto T Arai K Kinoshita M Hashimoto H Ozato K Wakamatsu Y 《Development, growth & differentiation》2007,49(9):699-709
Reprogramming of adult somatic cell nuclei to pluripotency has been unsuccessful in non-mammalian animals, primarily because of chromosomal aberrations in nuclear transplants, which are considered to be caused by asynchrony between the cell cycles of the recipient egg and donor nucleus. In order to normalize the chromosomal status, we used diploidized eggs by retention of second polar body release, instead of enucleated eggs, as recipients in nuclear transfer of primary culture cells from the caudal fin of adult green fluorescent protein gene (GFP) transgenic medaka fish (Oryzias latipes). We found that 2.7% of the reconstructed embryos grew into adults that expressed GFP in various tissues in the same pattern as in the donor fish. Moreover, these fish were diploid, fertile and capable of passing the marker gene to the next generation in Mendelian fashion. We hesitate to call these fish 'clones' because we used non-enucleated eggs as recipients; in effect, they may be chimeras consisting of cells derived from diploid recipient nuclei and donor nuclei. In either case, fish adult somatic cell nuclei were reprogrammed to pluripotency and differentiated into a variety of cell types including germ cells via the use of diploidized recipient eggs. 相似文献
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Moringa oleifera is a pantropical tree of the family Moringaceae. A previously undescribed property of an aqueous extract from the seeds of this plant is the modulation of ruminal fermentation patterns, especially protein degradation, as demonstrated in a short-term batch incubation system. Gas, short chain fatty acids (SCFA) and cellulolytic enzyme activities were determined as general fermentation parameters. A dot blot assay able to directly detect true protein in rumen fluid samples was used to quantify protein degradation. For complex substrates the interpretation of protein degradation profiles was amended by polyacrylamide gel electrophoresis (PAGE) of the samples. When incubated with pure carbohydrates at a concentration of 1 mg ml–1, the extract reduced microbial degradation of the model protein, bovine serum albumin (BSA), such that its concentration was at least 40% above the control after 12 h of incubation. Total protein degradation was thus delayed by approximately 9 h. When fermented along with wheat straw, leaf protein (Rubisco) was almost entirely protected during 12 h of fermentation. The degradation of soy proteins was retarded by at least 4- 6 h, depending on the protein band. There were strong side effects on the fermentation of pure cellulose (SCFA yield -60% after 12 h), whereas cellobiose and starch fermentation were less affected (-18 and -8%, respectively). When the complex substrates were fermented, SCFA yield was reduced by approximately 30% after 12 h. In our work we clearly demonstrate the efficacy of the new substance, which is neither a tannin nor a saponin, in an in vitro system, using pure as well as complex substrates. The properties shown in vitro for the crude extract suggest that it could have a positive effect on the protein metabolism of ruminants under intensive management and that negative side effects can be overcome by an optimized dosage. If the chemical nature of the active substance and its mechanism of action can be clarified, it may provide an alternative to replace critical synthetic feed additives (such as antibiotics) for high yielding dairy cows. 相似文献
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Molecular phylogenetic evidence that the phylum Haplosporidia has an alveolate ancestry 总被引:1,自引:0,他引:1
The phylogenetic position of the phylum Haplosporidia among other protists
was investigated with the complete 16S-like rRNA gene sequences from two
species in the phylum: Haplosporidium nelsoni, a parasite of oysters, and
Minchinia teredinis, a parasite of shipworms. Because the lack of obvious
morphological homologies with other protists hampered decisions regarding
taxonomic composition for sequence alignment and phylogenetic analysis, the
complete sequences for these two haplosporidians were directed as search
queries to the blast/ncbi.nlm.nih.gov electronic mail server. The results
of this heuristic similarity search provided a basis for constructing a
preliminary higher-taxonomic-level analysis comparing the haplosporidians
with species from the slime molds, fungi, algae, amoebae, ciliates,
dinoflagellates, and apicomplexans. Maximum parsimony yielded equivocal
results, whereas transversionally weighted parsimony suggested an affinity
with the alveolates (i.e., the ciliates, dinoflagellates, and
apicomplexans). Multiple alignment of the two haplosporidian sequences
against 17 taxa in a secondary analysis focusing on the alveolates and
subsequent parsimony analysis placed the phylum Haplosporidia as a
monophyletic group within the Alveolata and as a taxon of equal rank with
the other three alveolate phyla. The precise placement within the Alveolata
was sensitive to weighting.
相似文献
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