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71.
Pig to human xenotransplantation is considered a possible solution to the
prevailing chronic lack of human donor organs for allotransplantation. The
Galalpha1,3Gal determinant is the major porcine xenogeneic epitope causing
hyperacute rejection following human antibody binding and complement
activation. In order to characterize the tissue distribution of
Galalpha1,3Gal-containing and blood group- type glycosphingolipids in pig,
acid and nonacid glycosphingolipids were isolated from the kidney, small
intestine, spleen, salivary gland, liver, and heart of a single pig
obtained from a semi-inbred strain homozygous at the SLA locus. Glycolipids
were analyzed by thin-layer immunostaining using monoclonal antibodies, and
following ceramide glycanase cleavage as permethylated oligosaccharides by
gas chromatography, gas chromatography-mass spectrometry, and matrix-
assisted laser desorption/ionization mass spectrometry. The kidney
contained large amounts of Galalpha1,3Gal-containing penta- and
hexasaccharides having carbohydrate sequences consistent with the
Galalpha1,3nLc4and Galalpha1,3Lexstructures, respectively. The former
structure was tentatively identified in all organs by GC/MS. The presence
of extended Galalpha1,3Gal-terminated structures in the kidney and heart
was suggested by antibody binding, and GC/MS indicated the presence of a
Galalpha1,3nLc6structure in the heart. The kidney, spleen, and heart
contained blood group H pentaglycosylceramides based on type 1 (H-5-1) and
type 2 (H-5-2) chains, and H hexaglycosylceramides based on the type 4
chain (H-6-4). In the intestine H-5-1 and H-6-4 were expressed, in the
salivary gland H-5-1 and H-5-2, whereas only the H-5-1 structure was
identified in the liver. Blood group A structures were identified in the
salivary gland and the heart by antibody binding and GC/MS, indicating an
organ- specific expression of blood group AH antigens in the pig.
相似文献
72.
73.
James Riddell 《BMJ (Clinical research ed.)》1936,1(3928):792-793
74.
Kloverpris HN Stryhn A Harndahl M van der Stok M Payne RP Matthews PC Chen F Riddell L Walker BD Ndung'u T Buus S Goulder P 《Journal of virology》2012,86(2):919-929
The genetic polymorphism that has the greatest impact on immune control of human immunodeficiency virus (HIV) infection is expression of HLA-B*57. Understanding of the mechanism for this strong effect remains incomplete. HLA-B*57 alleles and the closely related HLA-B*5801 are often grouped together because of their similar peptide-binding motifs and HIV disease outcome associations. However, we show here that the apparently small differences between HLA-B*57 alleles, termed HLA-B*57 micropolymorphisms, have a significant impact on immune control of HIV. In a study cohort of >2,000 HIV C-clade-infected subjects from southern Africa, HLA-B*5703 is associated with a lower viral-load set point than HLA-B*5702 and HLA-B*5801 (medians, 5,980, 15,190, and 19,000 HIV copies/ml plasma; P = 0.24 and P = 0.0005). In order to better understand these observed differences in HLA-B*57/5801-mediated immune control of HIV, we undertook, in a study of >1,000 C-clade-infected subjects, a comprehensive analysis of the epitopes presented by these 3 alleles and of the selection pressure imposed on HIV by each response. In contrast to previous studies, we show that each of these three HLA alleles is characterized both by unique CD8(+) T-cell specificities and by clear-cut differences in selection pressure imposed on the virus by those responses. These studies comprehensively define for the first time the CD8(+) T-cell responses and immune selection pressures for which these protective alleles are responsible. These findings are consistent with HLA class I alleles mediating effective immune control of HIV through the number of p24 Gag-specific CD8(+) T-cell responses generated that can drive significant selection pressure on the virus. 相似文献
75.
Jun Pu Anthony F. Kreft Suzan H. Aschmies Kevin P. Atchison Joshua Berkowitz Thomas J. Caggiano Micheal Chlenov George Diamantidis Boyd L. Harrison Yun Hu Donna Huryn J. Steven Jacobsen Mei Jin Kerri Lipinski Peimin Lu Robert L. Martone Koi Morris June Sonnenberg-Reines Dave R. Riddell Joan Sabalski Lynn Resnick 《Bioorganic & medicinal chemistry》2009,17(13):4708-4717
γ-Secretase inhibitors have been shown to reduce the production of β-amyloid, a component of the plaques that are found in brains of patients with Alzheimer’s disease. A novel series of heterocyclic sulfonamide γ-secretase inhibitors that reduce β-amyloid levels in cells is reported. Several examples of compounds within this series demonstrate a higher propensity to inhibit the processing of amyloid precursor protein compared to Notch, an alternative γ-secretase substrate. 相似文献
76.
The objective was to determine the average amount of bovine viral diarrhea virus (BVDV) associated with single in vivo-derived and in vitro-produced bovine embryos following recommended processing procedures for embryos. In vivo-derived and in vitro-produced bovine embryos at 7 d post-fertilization were exposed (for 2 h) to 2 × 105-7 cell culture infective dose (CCID50)/mL of SD-1 (a noncytopathic, Type 1a strain of BVDV), and then washed according to International Embryo Transfer Society (IETS) guidelines prior to testing. Of the 87 in vivo-derived embryos tested, 27% were positive for virus by quantitative polymerase chain reaction (qPCR). The range in amount of virus associated with 99% of the contaminated embryos was ≤6.62 ± 1.57 copies/5 μL; 90% of the contaminated embryos had ≤4.64 ± 1.57 viral copies/5 μL of embryo-associated virus, using tolerance intervals (P < 0.05). The SEM was 0.33 and the mean of averages was 1.12/5 μL. Of the 87 in vitro-produced embryos, 42% were positive for virus. The range in amount of virus associated with 99% of the contaminated embryos was ≤3.44 ± 0.89 copies/5 μL; 90% of the contaminated embryos had ≤2.40 ± 0.89 viral copies/5 μL of embryo-associated virus using tolerance intervals (P < 0.05; S.E.M. was 0.14 and the mean of averages was 0.55/5 μL). Therefore, although many embryos were positive for virus, there were limited numbers of copies, thereby posing doubt regarding their potential for contamination following embryo transfer. 相似文献
77.
Gametes, somatic cells and materials of animal origin in media are potential sources for introducing bovine viral diarrhea virus (BVDV) into systems for production of IVF bovine embryos. Further, the efficacy of washing and trypsin treatment for removal of BVDV from IVF embryos is questionable. Washing and trypsin treatments recommended by the International Embryo Transfer Society for in vivo-derived embryos were applied to in vitro-derived, virus-exposed, bovine embryos in this side-by-side comparison of treatments. Embryos for the study were produced in a virus-free system in which follicular oocytes were matured and fertilized in vitro and presumptive zygotes were co-cultured with bovine uterine tubal cells for 7 d. A total of 18 trials was performed, 9 using a noncytopathic BVDV and 9 using a cytopathic BVDV. In each trial, 4 equal groups of 10 or less, zona pellucida-intact embryos/ova were assembled, including 2 groups of morulae and blastocysts (M/B) and 2 groups of nonfertile or degenerated ova (NFD). Each group was prewashed and exposed to 10(4) to 10(6) TCID50/mL of either noncytopathic (SD-1) or cytopathic (NADL) BVDV for 2 h. Following in vitro viral exposure, one group of M/B and one group of NFD were washed. The other groups of M/B and NFD were trypsin-treated. Both treatments were consistent with IETS guidelines. After in vitro exposure to noncytopathic BVDV and washing, viral assays of 100% (9/9) and 78% (7/9) of the groups of M/B and NFD ova, respectively, were positive. After in vitro exposure to cytopathic BVDV and washing, viral assay of 33% (3/9) of the groups of both M/B and NFD ova were positive. After in vitro exposure to noncytopathic BVDV and trypsin treatment, viral assay of 44% (4/9) of groups of M/B and 67% (6/9) of groups of NFD ova were positive. Finally, after in vitro exposure to cytopathic BVDV and trypsin treatment, viral assay of 22% (2/9) of the groups of M/B and 44% (4/9) of the groups of NFD ova were positive. Contingency table analysis, in which data was stratified by embryo type and virus biotype, was used to compare results. While a difference existed between results of the 2 treatments of groups of M/B within the noncytopathic biotype (P = 0.01, Mantel Haenszel Chi-square), no difference was observed between comparison of treatment between all groups in both biotypes (P > 0.05). 相似文献
78.
79.
Energy substrate utilization during prolonged exercise with and without carbohydrate intake in preadolescent and adolescent girls. 总被引:1,自引:0,他引:1
Little information is available on energy metabolism during exercise in girls, particularly the contribution of exogenous carbohydrate (CHO(exo)). The purpose of this study was to determine substrate utilization during exercise with and without CHO(exo) intake in healthy girls. Twelve-yr-old preadolescent (YG; n = 12) and 14-yr-old adolescent (OG; n = 10) girls consumed flavored water (WT) or (13)C-enriched 6% CHO (CT) while cycling for 60 min at approximately 70% maximal aerobic power (Vo(2max)). Substrate utilization was calculated for the final 15 min of exercise. CHO(exo) decreased fat oxidation by approximately 50% in YG but not in OG (P < 0.001) and decreased endogenous CHO oxidation by approximately 15% in OG but not in YG (P = 0.006). Endogenous CHO oxidation was lower in YG than in OG regardless of trial (P < or = 0.01), whereas fat oxidation was higher in YG only during WT (P < 0.001). CHO(exo) oxidation rate was similar between YG and OG (7.1 +/- 0.5 and 6.8 +/- 0.4 mg.kg(-1).min(-1), respectively, P = 0.67), contributing approximately 19% to total energy expenditure. Serum estradiol levels in all girls correlated with fat (r = -0.50 to -0.59, P = 0.03 to 0.005) and endogenous CHO oxidation (r = 0.50 to 0.63, P = 0.03 to 0.005) but not with CHO(exo) oxidation (r = -0.09, P = 0.71). We conclude that CHO(exo) influences endogenous substrate utilization in an age-dependent manner in healthy girls but that total CHO(exo) oxidation during exercise is not different between YG and OG. Our results also point to potential sex-related differences in energy substrate utilization even during childhood. 相似文献
80.
Riddell FG 《Chirality》2002,14(2-3):121-125
Recent progress in studies of the mechanism of transport of alkali metal ions by ionophoric antibiotics and the structures of alkali metal salts of the ionophores monensin and narasin is reviewed. The structures obtained from 2D NMR experiments in solution provide considerable insights into the mechanisms of transport. 相似文献