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51.
Prooxidant and antioxidant activities of bilirubin and its metabolic precursor biliverdin: a structure-activity study 总被引:3,自引:0,他引:3
Bilirubin, which is derived from its metabolic precursor biliverdin, is the end product of heme catabolism. It has been proposed as a physiological antioxidant present in human extracellular fluids. We have earlier shown that bilirubin in the presence of the transition metal ion Cu(II) causes strand cleavage in DNA through generation of reactive oxygen species, particularly the hydroxyl radical. Thus bilirubin possesses both antioxidant and prooxidant properties. In order to understand the chemical basis of various biological properties of bilirubin, we have studied the structure-activity relationship between bilirubin and its precursor biliverdin. The latter has also been reported to possess both antioxidant and toxic properties. In the present studies bilirubin was found to be more effective in the DNA cleavage reaction and a more efficient reducer of Cu(II). The rate of formation of hydrogen peroxide and hydroxyl radicals by the compounds also showed a similar pattern. The relative antioxidant activity was also examined by studying the effect of these compounds on DNA cleavage by a hydroxyl radical generating system and their quenching effect on hydroxyl radicals. The results indicate that bilirubin is more active both as an antioxidant as well as an oxidative DNA cleaving agent. A model for binding of copper to bilirubin has been proposed where two copper ions are bound to two molecules of bilirubin through their terminal pyrrole nitrogens. In order to account for the enhanced copper reducing capacity of bilirubin we have further proposed that an additional copper binding site is provided for in the case of bilirubin due to the absence of a double bond between pyrrole rings II and III. Further it would appear that the structural features of the bilirubin molecule which are important for its prooxidant action are also the ones that render it a more effective antioxidant. 相似文献
52.
BACKGROUND: A number of reports indicate that circulating immune complexes (CIC) and activation of the complement system contribute to the pathogenesis of Type I allergy. The aim of this study was to investigate the status of CIC in 113 patients with rhinitis in Lebanon and determine complement components C3 and C4 serum levels in the CIC-positive patients. Serum specific IgE antibodies were previously detected and reported in 74 of the 113 patients. METHODS: CIC were detected by polyethylene glycol precipitation and serum C3 and C4 levels quantified by radial immunodiffusion. RESULTS: CIC was positive in 20 of the specific IgE-positive and 13 of the specific IgE-negative patients. C3 and C4 levels were within the normal range in all the 33 CIC-positive patients. CONCLUSIONS: The antibody class that constitutes the complexes does not seem to be IgG or IgM. Moreover, complement activation does not seem to be involved in the allergic reaction since both C3 and C4 levels were normal in all patients. The role of these complexes, if any, in the pathogenesis of rhinitis is yet to be determined. 相似文献
53.
Ansari-Lari M Saadat M Hadi N 《Biochemical and biophysical research communications》2003,312(2):299-302
Workers in the petroleum distribution trades experience relatively low-level exposures to gasoline vapors whose consequences have not been fully elucidated. The purpose of this study was to investigate changes in the hematological parameters among filling station workers who were occupationally exposed to gasoline. The target group for the study consisted of 41 workers from eight filling stations of Shiraz (south of Iran). The control group consisted of 27 healthy subjects matched for age and sex from general population. The complete blood count analysis was done in one laboratory. Using PCR-based method, the genotypes of glutathione S-transferase T1 (GSTT1) and M1 (GSTM1) were determined. Workers were divided into three exposure groups according to employment history: duration less than 1 year, 1-5 years, and more than 5 years. Comparison was performed using Kruskal-Wallis test. In the individuals with the presence of both GSTT1 and GSTM1 functional alleles, comparison between four exposure groups revealed no significant difference for studied hematological variables. There were statistically significant differences between study groups, with only one functional allele, either GSTT1 or GSTM1, for relative number of lymphocytes (chi(2)=9.147, df=3, P=0.027) and neutrophils (chi(2)=9.951, df=3, and P=0.019), and absolute number of lymphocytes (chi(2)=9.135, df=3, and P=0.028), and RBC (chi(2)=10.586, df=3, and P=0.014). These findings could indicate the possible protective effect of concurrent presence of GSTM1 and GSTT1 enzymes on the hematopoietic system of filling station workers. 相似文献
54.
In a search for immunogenic virulence factors in Neisseria meningitidis, we have identified a gene encoding a predicted 160 kDa protein with homology to the autotransporter family of proteins. Members of this family are secreted or surface exposed and are often associated with virulence in Gram-negative bacterial pathogens. We named the gene adhesion and penetration protein (app), because of its extensive homology to the hap gene of Haemophilus influenzae. We reconstructed the gene with reference to genomic sequence data and cloned and expressed the protein in Escherichia coli. Rabbit antiserum raised against recombinant App reacted with proteins in all meningococcal isolates examined, which represented clonal groups responsible for the majority of meningococcal invasive disease. Antibodies to the protein were detected in the sera of patients convalescing from meningococcal infection. Purified App had strong stimulating activity for T cells isolated from a number of healthy donors and from one convalescent patient. We confirmed that App is surface localized, cleaved and secreted by N. meningitidis. Importantly, the rabbit anti-App serum killed the organism in the presence of complement. Thus, App is conserved among meningococci, immunogenic in humans and potentially involved in virulence. It therefore merits further investigation as a component of a future multivalent vaccine. 相似文献
55.
Abd H Johansson T Golovliov I Sandström G Forsman M 《Applied and environmental microbiology》2003,69(1):600-606
Francisella tularensis is a highly infectious, facultative intracellular bacterium which causes epidemics of tularemia in both humans and mammals at regular intervals. The natural reservoir of the bacterium is largely unknown, although it has been speculated that protozoa may harbor it. To test this hypothesis, Acanthamoeba castellanii was cocultured with a strain of F. tularensis engineered to produce green fluorescent protein (GFP) in a nutrient-rich medium. GFP fluorescence within A. castellanii was then monitored by flow cytometry and fluorescence microscopy. In addition, extracellular bacteria were distinguished from intracellular bacteria by targeting with monoclonal antibodies. Electron microscopy was used to determine the intracellular location of F. tularensis in A. castellanii, and viable counts were obtained for both extracellular and intracellular bacteria. The results showed that many F. tularensis cells were located intracellularly in A. castellanii cells. The bacteria multiplied within intracellular vacuoles and eventually killed many of the host cells. F. tularensis was found in intact trophozoites, excreted vesicles, and cysts. Furthermore, F. tularensis grew faster in cocultures with A. castellanii than it did when grown alone in the same medium. This increase in growth was accompanied by a decrease in the number of A. castellanii cells. The interaction between F. tularensis and amoebae demonstrated in this study indicates that ubiquitous protozoa might be an important environmental reservoir for F. tularensis. 相似文献
56.
Calcineurin (CnA) is an important signalling molecule in skeletal muscle, in the promotion of differentiation, slow-fibre phenotype and possibly fibre hypertrophy. We found that stable expression of constitutively active CnA in muscle C2C12 cells strongly activated NF-kappaB, a key mediator of muscle wasting. NF-kappaB activation by CnA was associated with elevated phospho-IkappaBalpha, and could be repressed by specific genetic (porZAKI-4 and porDSCR1) and chemical (cyclosporin A) inhibitors of CnA, but tumour necrosis factor-alpha (TNF-alpha) appeared not to be a key component in the cross-talk. Functionally, CnA-induced NF-kappaB activation seemed to interfere with terminal muscle differentiation. We therefore showed a functional interaction between the CnA and NF-kappaB pathways in skeletal muscle cells, which involved opposing phenotypic effects of CnA. 相似文献
57.
58.
Mahdi Maktabdar Oghaz Mohd Aizaini Maarof Anazida Zainal Mohd Foad Rohani S. Hadi Yaghoubyan 《PloS one》2015,10(8)
Color is one of the most prominent features of an image and used in many skin and face detection applications. Color space transformation is widely used by researchers to improve face and skin detection performance. Despite the substantial research efforts in this area, choosing a proper color space in terms of skin and face classification performance which can address issues like illumination variations, various camera characteristics and diversity in skin color tones has remained an open issue. This research proposes a new three-dimensional hybrid color space termed SKN by employing the Genetic Algorithm heuristic and Principal Component Analysis to find the optimal representation of human skin color in over seventeen existing color spaces. Genetic Algorithm heuristic is used to find the optimal color component combination setup in terms of skin detection accuracy while the Principal Component Analysis projects the optimal Genetic Algorithm solution to a less complex dimension. Pixel wise skin detection was used to evaluate the performance of the proposed color space. We have employed four classifiers including Random Forest, Naïve Bayes, Support Vector Machine and Multilayer Perceptron in order to generate the human skin color predictive model. The proposed color space was compared to some existing color spaces and shows superior results in terms of pixel-wise skin detection accuracy. Experimental results show that by using Random Forest classifier, the proposed SKN color space obtained an average F-score and True Positive Rate of 0.953 and False Positive Rate of 0.0482 which outperformed the existing color spaces in terms of pixel wise skin detection accuracy. The results also indicate that among the classifiers used in this study, Random Forest is the most suitable classifier for pixel wise skin detection applications. 相似文献
59.
The type and frequency of structural hemoglobin variants and their hematological and molecular characteristics were identified
using PCR-RFLP and sequencing techniques in 66 individuals from 33 unrelated families who referred to the two clinics of Kermanshah
University of Medical Sciences from 2005 to 2006. We detected 28 subjects carrier for Hb D-Punjab (42.4%), 21 individuals
carrier of Hb Q-Iran (31.8%), 12 subjects heterozygous for Hb Setif (18.2%), four cases with sickle cell disease (6.1%), and
one case with Hb C (1.5%). All βS genes (4 genes) were linked to the Benin haplotype with negative Taq I site 5′ to γA gene. All βD-Punjab genes (29 genes) were in linkage disequilibrium with haplotype I. The only βC chromosome was linked to haplotype II. Both β0-thalassemia chromosomes with CD15 (G → A) mutation had haplotype background I. Three β+-thalassemia chromosomes with IVSI.110 (G → A) mutation were associated with haplotype I [+ − − − − + +]. In turn, the three
β-thalassemia chromosomes with IVS II.1 G → A mutation were associated with atypical haplotype [− + + + + + −]. Hematological
indices of carriers of Hb D-Punjab, Hb Q-Iran and Hb Setif were lower than those reported for normal individuals. For the
first time, we have reported the haplotype background of βS gene among Kurdish population of Iran. Our results revealed that Hb D-Punjab is the most prevalent β-globin chain structural
variant in this area and that is followed in frequency by an α-chain variant, Hb Q-Iran. The result of present study is useful
for clinical management and the establishment of screening programmes in Western Iran. 相似文献
60.
Yusuke Hirasawa Tomokazu Shoji Takashi Arai Alfarius E. Nugroho Jun Deguchi Takahiro Hosoya Nahoko Uchiyama Yukihiro Goda Khalijah Awang A. Hamid A. Hadi Motoo Shiro Hiroshi Morita 《Bioorganic & medicinal chemistry letters》2010,20(6):2021-2024
A new bisindole alkaloid, bisleuconothine A (1) consisting of an eburnane–aspidosperma type skeleton, was isolated from the bark of Leuconotis griffithii. The structure including absolute stereochemistry was elucidated on the basis of 2D NMR data and X-ray analysis. Bisleuconothine A (1) showed cell growth inhibitory activity against various human cancer cell lines. 相似文献