全文获取类型
收费全文 | 460篇 |
免费 | 40篇 |
出版年
2022年 | 3篇 |
2021年 | 16篇 |
2020年 | 3篇 |
2019年 | 8篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 17篇 |
2015年 | 31篇 |
2014年 | 25篇 |
2013年 | 29篇 |
2012年 | 25篇 |
2011年 | 17篇 |
2010年 | 16篇 |
2009年 | 15篇 |
2008年 | 15篇 |
2007年 | 16篇 |
2006年 | 30篇 |
2005年 | 12篇 |
2004年 | 21篇 |
2003年 | 9篇 |
2002年 | 10篇 |
2001年 | 5篇 |
2000年 | 16篇 |
1999年 | 10篇 |
1998年 | 12篇 |
1997年 | 5篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1992年 | 8篇 |
1991年 | 2篇 |
1990年 | 10篇 |
1989年 | 6篇 |
1988年 | 13篇 |
1987年 | 6篇 |
1986年 | 8篇 |
1985年 | 12篇 |
1984年 | 2篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1981年 | 5篇 |
1980年 | 2篇 |
1979年 | 5篇 |
1977年 | 4篇 |
1975年 | 3篇 |
1974年 | 1篇 |
1971年 | 1篇 |
1970年 | 2篇 |
1969年 | 2篇 |
1967年 | 2篇 |
1966年 | 1篇 |
排序方式: 共有500条查询结果,搜索用时 31 毫秒
41.
Ooi H Cadogan E Sweeney M Howell K O'Regan RG McLoughlin P 《American journal of physiology. Heart and circulatory physiology》2000,278(2):H331-H338
Chronic hypercapnia is commonly found in patients with severe hypoxic lung disease and is associated with a greater elevation of pulmonary arterial pressure than that due to hypoxia alone. We hypothesized that hypercapnia worsens hypoxic pulmonary hypertension by augmenting pulmonary vascular remodeling and hypoxic pulmonary vasoconstriction (HPV). Rats were exposed to chronic hypoxia [inspiratory O(2) fraction (FI(O(2))) = 0.10], chronic hypercapnia (inspiratory CO(2) fraction = 0.10), hypoxia-hypercapnia (FI(O(2)) = 0.10, inspiratory CO(2) fraction = 0.10), or room air. After 1 and 3 wk of exposure, muscularization of resistance blood vessels and hypoxia-induced hematocrit elevation were significantly inhibited in hypoxia-hypercapnia compared with hypoxia alone (P < 0.001, ANOVA). Right ventricular hypertrophy was reduced in hypoxia-hypercapnia compared with hypoxia at 3 wk (P < 0.001, ANOVA). In isolated, ventilated, blood-perfused lungs, basal pulmonary arterial pressure after 1 wk of exposure to hypoxia (20.1 +/- 1.8 mmHg) was significantly (P < 0.01, ANOVA) elevated compared with control conditions (12.1 +/- 0.1 mmHg) but was not altered in hypoxia-hypercapnia (13.5 +/- 0.9 mmHg) or hypercapnia (11.8 +/- 1.3 mmHg). HPV (FI(O(2)) = 0.03) was attenuated in hypoxia, hypoxia-hypercapnia, and hypercapnia compared with control (P < 0.05, ANOVA). Addition of N(omega)-nitro-L-arginine methyl ester (10(-4) M), which augmented HPV in control, hypoxia, and hypercapnia, significantly reduced HPV in hypoxia-hypercapnia. Chronic hypoxia caused impaired endothelium-dependent relaxation in isolated pulmonary arteries, but coexistent hypercapnia partially protected against this effect. These findings suggest that coexistent hypercapnia inhibits hypoxia-induced pulmonary vascular remodeling and right ventricular hypertrophy, reduces HPV, and protects against hypoxia-induced impairment of endothelial function. 相似文献
42.
Higashi T Miura K Kikuchi R Shimada K Hiyamizu H Ooi H Iwabuchi Y Hatakeyama S Kubodera N 《Steroids》2000,65(5):281-294
The characterization of new conjugated vitamin D metabolites in rat bile was performed using HPLC, liquid chromatography/tandem mass spectrometry combined derivatization, and GC-MS. After the administration of 24,25-dihydroxyvitamin D(3) to rats, 23, 25-dihydroxy-24-oxovitamin D(3) 23-glucuronide, 3-epi-24, 25-dihydroxyvitamin D(3) 24-glucuronide, and 24,25-dihydroxyvitamin D(3) 3-sulfate were obtained as new biliary metabolites together with 24,25-dihydroxyvitamin D(3) 3- and 24-glucuronides. The above metabolites, except 24,25-dihydroxyvitamin D(3) 3-glucuronide, were obtained from rats dosed with 25-hydroxyvitamin D(3). 23, 25-Dihydroxyvitamin D(3) 23-glucuronide was also obtained from the bile of rats administered 25-hydroxyvitamin D(3) in addition to its 3-glucuronide, 25-glucuronide, and 3-sulfate. Thus, it was found that 24,25-dihydroxyvitamin D(3) and 25-hydroxyvitamin D(3) were directly conjugated as glucuronide and sulfate, whereas at the C-23 position, they were hydroxylated and then conjugated. Furthermore, we found that the C-3 epimerization acts as one of the important pathways in vitamin D metabolism. 相似文献
43.
Out of Africa and back again: nested cladistic analysis of human Y chromosome variation 总被引:18,自引:3,他引:15
Hammer MF; Karafet T; Rasanayagam A; Wood ET; Altheide TK; Jenkins T; Griffiths RC; Templeton AR; Zegura SL 《Molecular biology and evolution》1998,15(4):427-441
We surveyed nine diallelic polymorphic sites on the Y chromosomes of 1,544
individuals from Africa, Asia, Europe, Oceania, and the New World.
Phylogenetic analyses of these nine sites resulted in a tree for 10
distinct Y haplotypes with a coalescence time of approximately 150,000
years. The 10 haplotypes were unevenly distributed among human populations:
5 were restricted to a particular continent, 2 were shared between Africa
and Europe, 1 was present only in the Old World, and 2 were found in all
geographic regions surveyed. The ancestral haplotype was limited to African
populations. Random permutation procedures revealed statistically
significant patterns of geographical structuring of this paternal genetic
variation. The results of a nested cladistic analysis indicated that these
geographical associations arose through a combination of processes,
including restricted, recurrent gene flow (isolation by distance) and range
expansions. We inferred that one of the oldest events in the nested
cladistic analysis was a range expansion out of Africa which resulted in
the complete replacement of Y chromosomes throughout the Old World, a
finding consistent with many versions of the Out of Africa Replacement
Model. A second and more recent range expansion brought Asian Y chromosomes
back to Africa without replacing the indigenous African male gene pool.
Thus, the previously observed high levels of Y chromosomal genetic
diversity in Africa may be due in part to bidirectional population
movements. Finally, a comparison of our results with those from nested
cladistic analyses of human mtDNA and beta-globin data revealed different
patterns of inferences for males and females concerning the relative roles
of population history (range expansions) and population structure
(recurrent gene flow), thereby adding a new sex-specific component to
models of human evolution.
相似文献
44.
Tara?Clinton-McHarg Sze?Lin?Yoong Flora?Tzelepis Tim?Regan Alison?Fielding Eliza?Skelton Melanie?Kingsland Jia?Ying?Ooi Luke?WolfendenEmail author 《Implementation science : IS》2015,11(1):148
Background
Recent reviews have synthesised the psychometric properties of measures developed to examine implementation science constructs in healthcare and mental health settings. However, no reviews have focussed primarily on the properties of measures developed to assess innovations in public health and community settings. This review identified quantitative measures developed in public health and community settings, examined their psychometric properties, and described how the domains of each measure align with the five domains and 37 constructs of the Consolidated Framework for Implementation Research (CFIR).Methods
MEDLINE, PsycINFO, EMBASE, and CINAHL were searched to identify publications describing the development of measures to assess implementation science constructs in public health and community settings. The psychometric properties of each measure were assessed against recommended criteria for validity (face/content, construct, criterion), reliability (internal consistency, test-retest), responsiveness, acceptability, feasibility, and revalidation and cross-cultural adaptation. Relevant domains were mapped against implementation constructs defined by the CFIR.Results
Fifty-one measures met the inclusion criteria. The majority of these were developed in schools, universities, or colleges and other workplaces or organisations. Overall, most measures did not adequately assess or report psychometric properties. Forty-six percent of measures using exploratory factor analysis reported >50 % of variance was explained by the final model; none of the measures assessed using confirmatory factor analysis reported root mean square error of approximation (<0.06) or comparative fit index (>0.95). Fifty percent of measures reported Cronbach’s alpha of <0.70 for at least one domain; 6 % adequately assessed test-retest reliability; 16 % of measures adequately assessed criterion validity (i.e. known-groups); 2 % adequately assessed convergent validity (r?>?0.40). Twenty-five percent of measures reported revalidation or cross-cultural validation. The CFIR constructs most frequently assessed by the included measures were relative advantage, available resources, knowledge and beliefs, complexity, implementation climate, and other personal resources (assessed by more than ten measures). Five CFIR constructs were not addressed by any measure.Conclusions
This review highlights gaps in the range of implementation constructs that are assessed by existing measures developed for use in public health and community settings. Moreover, measures with robust psychometric properties are lacking. Without rigorous tools, the factors associated with the successful implementation of innovations in these settings will remain unknown45.
Jalal Rouhi Mohamad Hafiz Mamat C. H. Raymond Ooi Shahrom Mahmud Mohamad Rusop Mahmood 《PloS one》2015,10(4)
High-density and well-aligned ZnO–ZnS core–shell nanocone arrays were synthesized on fluorine-doped tin oxide glass substrate using a facile and cost-effective two-step approach. In this synthetic process, the ZnO nanocones act as the template and provide Zn2+ ions for the ZnS shell formation. The photoluminescence spectrum indicates remarkably enhanced luminescence intensity and a small redshift in the UV region, which can be associated with the strain caused by the lattice mismatch between ZnO and ZnS. The obtained diffuse reflectance spectra show that the nanocone-based heterostructure reduces the light reflection in a broad spectral range and is much more effective than the bare ZnO nanocone and nanorod structures. Dye-sensitized solar cells based on the heterostructure ZnO–ZnS nanocones are assembled, and high conversion efficiency (η) of approximately 4.07% is obtained. The η improvement can be attributed primarily to the morphology effect of ZnO nanocones on light-trapping and effectively passivating the interface surface recombination sites of ZnO nanocones by coating with a ZnS shell layer. 相似文献
46.
Characterization of thermostable FMN-dependent NADH azoreductase from the moderate thermophile Geobacillus stearothermophilus 总被引:1,自引:0,他引:1
Ken’ichiro Matsumoto Yuichi Mukai Daiki Ogata Fumi Shozui John Masani Nduko Seiichi Taguchi Toshihiko Ooi 《Applied microbiology and biotechnology》2010,86(5):1431-1438
The gene encoding an FMN-dependent NADH azoreductase, AzrG, from thermophilic Geobacillus stearothermophilus was cloned and functionally expressed in recombinant Escherichia coli. Purified recombinant AzrG is a homodimer of 23 kDa and bore FMN as a flavin cofactor. The optimal temperature of AzrG was
85 °C for the degradation of Methyl Red (MR). AzrG remained active for 1 h at 65 °C and for 1 month at 30 °C, demonstrating
both superior thermostability and long-term stability of the enzyme. AzrG efficiently decolorized MR, Ethyl Red at 30 °C.
Furthermore, the enzyme exhibited a wide-range of degrading activity towards several tenacious azo dyes, such as Acid Red
88, Orange I, and Congo Red. These results suggested the sustainable utilization of G. stearothermophilus as an azo-degrading strain for AzrG carrying whole-cell wastewater treatments for azo pollutants under high temperature conditions. 相似文献
47.
Linda S. M. Ooi Wing-Shan Ho Karry L. K. Ngai Li Tian Paul K. S. Chan Samuel S. M. Sun Vincent E. C. Ooi 《Journal of biosciences》2010,35(1):95-103
A mannose-binding lectin (Narcissus tazetta lectin [NTL]) with potent antiviral activity was isolated and purified from the bulbs of the Chinese daffodil Narcissus tazetta var. chinensis, using ion exchange chromatography on diethylaminoethyl (DEAE)-cellulose, affinity chromatography on mannose-agarose and
fast protein liquid chromatography (FPLC)-gel filtration on Superose 12. The purified lectin was shown to have an apparent
molecular mass of 26 kDa by gel filtration and 13 kDa by SDS-PAGE, indicating that it is probably a dimer with two identical
subunits. The cDNA-derived amino acid sequence of NTL as determined by molecular cloning also reveals that NTL protein contains
a mature polypeptide consisting of 105 amino acids and a C-terminal peptide extension. Three-dimensional modelling study demonstrated
that the NTL primary polypeptide contains three subdomains, each with a conserved mannose-binding site. It shows a high homology
of about 60%–80% similarity with the existing monocot mannose-binding lectins. NTL could significantly inhibit plaque formation
by the human respiratory syncytial virus (RSV) with an IC50 of 2.30 μg/ml and exhibit strong antiviral properties against influenza A (H1N1, H3N2, H5N1) and influenza B viruses with
IC50 values ranging from 0.20 μg/ml to 1.33 μg/ml in a dose-dependent manner. It is worth noting that the modes of antiviral action
of NTL against RSV and influenza A virus are significantly different. NTL is effective in the inhibition of RSV during the
whole viral infection cycle, but the antiviral activity of NTL is mainly expressed at the early stage of the viral cycle of
influenza A (H1N1) virus. NTL with a high selective index (SI=CC50/IC50≥141) resulting from its potent antiviral activity and low cytotoxicity demonstrates a potential for biotechnological development
as an antiviral agent. 相似文献
48.
A directed approach for engineering conditional protein stability using biologically silent small molecules 总被引:4,自引:0,他引:4
Maynard-Smith LA Chen LC Banaszynski LA Ooi AG Wandless TJ 《The Journal of biological chemistry》2007,282(34):24866-24872
The ability to regulate the function of specific proteins using cell-permeable molecules can be a powerful method for interrogating biological systems. To bring this type of "chemical genetic" control to a wide range of proteins, we recently developed an experimental system in which the stability of a small protein domain expressed in mammalian cells depends on the presence of a high affinity ligand. This ligand-dependent stability is conferred to any fused partner protein. The FK506- and rapamycin-binding protein (FKBP12) has been the subject of extensive biophysical analyses, including both kinetic and thermodynamic studies of the wild-type protein as well as dozens of mutants. The goal of this study was to determine if the thermodynamic stabilities (DeltaDeltaG(U-F)) of various amino acid substitutions within a given protein are predictive for engineering additional ligand-dependent destabilizing domains. We used FKBP12 as a model system and found that in vitro thermodynamic stability correlates weakly with intracellular degradation rates of the mutants and that the ability of a given mutation to destabilize the protein is context-dependent. We evaluated several new FKBP12 ligands for their ability to stabilize these mutants and found that a cell-permeable molecule called Shield-1 is the most effective stabilizing ligand. We then performed an unbiased microarray analysis of NIH3T3 cells treated with various concentrations of Shield-1. These studies show that Shield-1 does not elicit appreciable cellular responses. 相似文献
49.
Grousson N Lim KH Lim HS Ooi ET Salgues SL Yeo JH Goetz WA 《Journal of biomechanics》2007,40(10):2167-2173
With advances in tissue engineering and improvement of surgical techniques, stentless biological valves and valve-sparing procedures have become alternatives to traditional aortic valve replacement with stented bioprostheses or mechanical valves. New surgical techniques preserve the advantages of native valves but require better understanding of the anatomical structure of the aortic root. Silicone rubber was injected in fresh aortic roots of nine human cadavers under the physiological closing pressure of 80 mmHg. The casts reproduced every detail of the aortic root anatomy and were used to digitize 27 leaflet attachment lines (LALs) of the aortic valves. LALs were normalized and described with a mathematical model. LALs were found to follow a pattern with the right coronary being the largest followed by the non-coronary and then the left coronary. During diastole, the aortic valve LAL can be described by an intersection between a created tube and an extruded parabolic surface. This geometrical definition of the LAL during end diastole gives a better understanding of the aortic root anatomy and could be useful for heart valve design and improvement of aortic valve reconstruction technique. 相似文献
50.
Saito N Konishi K Ohta S Kondo T Kato M Hashino S Takeda H Asaka M Ooi HK 《Human cell》2007,20(1):10-14
A 44-year-old man was found to have M-proteins of IgG consisting of kappa- and lambda-chains in serum without lymphadenopathy or splenomegaly. The serum concentrations of IgG, IgA and IgM were within normal limits. Bone marrow examination showed normal cellular marrow containing 6.3% of plasma cells with no abnormal features. No chromosomal abnormality was observed at all. The patient was diagnosed as having monoclonal gammopathy of undetermined significance. The bone marrow plasma cells possessed free kappa- and lambda-chains in Golgi apparatus, rough endoplasmic reticula and cytoplasmic matrices. Plural light chains were simultaneously produced with the same heavy chain in a plasma cell by immunoelectron microscopy. This is the first report in the world of a monoclonal gammopathy of undetermined significance producing plural light chains with the same heavy chain. 相似文献