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81.
Moritoshi Iwagami Seung-Young Hwang So-Hee Kim So-Jung Park Ga-Young Lee Emilie Louise Akiko Matsumoto-Takahashi Weon-Gyu Kho Shigeyuki Kano 《PLoS neglected tropical diseases》2013,7(10)
Background
Vivax malaria was successfully eliminated in the Republic of Korea (South Korea) in the late 1970s, but it was found to have re-emerged from 1993. In order to control malaria and evaluate the effectiveness of malaria controls, it is important to develop a spatiotemporal understanding of the genetic structure of the parasite population. Here, we estimated the population structure and temporal dynamics of the transmission of Plasmodium vivax in South Korea by analyzing microsatellite DNA markers of the parasite.Methodology/Principal Findings
We analyzed 14 microsatellite DNA loci of the P. vivax genome from 163 South Korean isolates collected from 1994 to 2008. Allelic data were used to analyze linkage disequilibrium (LD), genetic differentiation and population structure, in order to make a detailed estimate of temporal change in the parasite population. The LD analysis showed a gradual decrease in LD levels, while the levels of genetic differentiation between successive years and analysis of the population structure based on the Bayesian approach suggested that a drastic genetic change occurred in the South Korean population during 2002 and 2003.Conclusions/Significance
Although relapse and asymptomatic parasite carriage might influence the population structure to some extent, our results suggested the continual introduction of P. vivax into South Korea through other parasite population sources. One possible source, particularly during 2002 and 2003, is North Korea. Molecular epidemiology using microsatellite DNA of the P. vivax population is effective for assessing the population structure and temporal dynamics of parasite transmission; information that can assist in the elimination of vivax malaria in endemic areas. 相似文献82.
Nancy Ciesla Victor Dinglas Eddy Fan Michelle Kho Jill Kuramoto Dale Needham 《Journal of visualized experiments : JoVE》2011,(50)
Survivors of acute respiratory distress syndrome (ARDS) and other causes of critical illness often have generalized weakness, reduced exercise tolerance, and persistent nerve and muscle impairments after hospital discharge.1-6 Using an explicit protocol with a structured approach to training and quality assurance of research staff, manual muscle testing (MMT) is a highly reliable method for assessing strength, using a standardized clinical examination, for patients following ARDS, and can be completed with mechanically ventilated patients who can tolerate sitting upright in bed and are able to follow two-step commands. 7, 8This video demonstrates a protocol for MMT, which has been taught to ≥43 research staff who have performed >800 assessments on >280 ARDS survivors. Modifications for the bedridden patient are included. Each muscle is tested with specific techniques for positioning, stabilization, resistance, and palpation for each score of the 6-point ordinal Medical Research Council scale.7,9-11 Three upper and three lower extremity muscles are graded in this protocol: shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension, and ankle dorsiflexion. These muscles were chosen based on the standard approach for evaluating patients for ICU-acquired weakness used in prior publications. 1,2. Download video file.(60M, mov) 相似文献
83.
Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network
Crosslin DR McDavid A Weston N Nelson SC Zheng X Hart E de Andrade M Kullo IJ McCarty CA Doheny KF Pugh E Kho A Hayes MG Pretel S Saip A Ritchie MD Crawford DC Crane PK Newton K Li R Mirel DB Crenshaw A Larson EB Carlson CS Jarvik GP;Electronic Medical Records Genomics 《Human genetics》2012,131(4):639-652
White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value?=?6.71e-55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy-/-). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn's disease. 相似文献
84.
Judith N. Haslett Peter B. Kang Mei Han Alvin T. Kho Despina Sanoudou Jay M. Volinski Alan H. Beggs Isaac S. Kohane Louis M. Kunkel 《Mammalian genome》2005,16(10):739-748
The phenotypic differences among Duchenne muscular dystrophy patients, mdx mice, and mdx5cv mice suggest that despite the common etiology of dystrophin deficiency, secondary mechanisms have a substantial influence
on phenotypic severity. The differential response of various skeletal muscles to dystrophin deficiency supports this hypothesis.
To explore these differences, gene expression profiles were generated from duplicate RNA targets extracted from six different
skeletal muscles (diaphragm, soleus, gastrocnemius, quadriceps, tibialis anterior, and extensor digitorum longus) from wild-type,
mdx, and mdx5cv mice, resulting in 36 data sets for 18 muscle samples. The data sets were compared in three different ways: (1) among wild-type
samples only, (2) among all 36 data sets, and (3) between strains for each muscle type. The molecular profiles of soleus and
diaphragm separate significantly from the other four muscle types and from each other. Fiber-type proportions can explain
some of these differences. These variations in wild-type gene expression profiles may also reflect biomechanical differences
known to exist among skeletal muscles. Further exploration of the genes that most distinguish these muscles may help explain
the origins of the biomechanical differences and the reasons why some muscles are more resistant than others to dystrophin
deficiency.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users.
Judith N. Haslett, Peter B. Kang These authors contributed equally to this work. 相似文献
85.
Petricka JJ Clay NK Nelson TM 《The Plant journal : for cell and molecular biology》2008,56(2):251-263
Leaf veins form a closed network that transports essential photosynthates, water and signaling molecules to the developing plant. The formation of the patterns of these networks during leaf ontogeny is an active subject of modeling and computer simulation. To investigate the vein patterning process, we performed screens for defects in juvenile leaf vein patterning in Arabidopsis thaliana lines subjected to mutagenesis via diepoxybutane, activation tagging or the Dissociation/Activator transposon. We identified over 40 vein pattern defective lines, providing a phenotypic resource for the testing of vein patterning models. In addition, we report the chromosomal linkage for 13 of these, eight of which were successfully cloned. We further describe the phenotypes of five of these mutants, which we call the defectively organized tributaries (dot) mutants, and their corresponding molecular identities. The diversity of the individual genes affected in this collection of pattern mutants suggests that vein pattern is highly sensitive to perturbations in many cellular processes. Despite this diversity of causes, the resulting pattern defects fall into a limited number of classes, including parallel, spurred, misaligned, open, midvein gap and irregularly spaced. These classes may represent sensitivities to cellular processes associated with the DOT genes. The ontogeny of common defective patterns should be accommodated into any robust model for the ontogeny and evolution of pattern. 相似文献
86.
Two new genotypes of Plasmodium vivax circumsporozoite protein found in the Republic of Korea 总被引:1,自引:0,他引:1
Kho WG Park YH Chung JY Kim JP Hong ST Lee WJ Kim TS Lee JS 《The Korean journal of parasitology》1999,37(4):265-270
The gene encoding Plasmodium vivax circumsporozoite protein (PvCSP) exhibits polymorphism in many geographical isolates. The present study was designed to investigate polymorphism in PvCSP gene of P. vivax isolates in Korea. Thirty isolates, obtained from indigenous cases in Yonchon-gun, Kyonggi-do in 1997, were subjected for sequencing and RFLP analysis of the repeat and post-repeat regions of PvCSP gene and two genotypes (SK-A and SK-B) were identified. The genotype of 19 isolates was SK-A and that of 11 isolates was SK-B. Although the number of 12-base repeats present in SK-A was three while two were found in a Chinese strain CH-5, the repeat sequence of SK-A was identical to that of CH-5 except for one base substitution. Compared with known data there was no identical isolates with SK-B, but the sequence of SK-B was similar to that of a North Korean (NK) isolate. These results indicate that two genotypes of PvCSP coexist in the present epidemic area of Korea and the present parasite may originate from East Asia. RFLP would be useful to classify genotypes of P. vivax population instead of gene sequencing. 相似文献
87.
Lennon NJ Kho A Bacskai BJ Perlmutter SL Hyman BT Brown RH 《The Journal of biological chemistry》2003,278(50):50466-50473
Mutations in the dysferlin gene cause limb girdle muscular dystrophy type 2B and Miyoshi myopathy. We report here the results of expression profile analyses and in vitro investigations that point to an interaction between dysferlin and the Ca2+ and lipid-binding proteins, annexins A1 and A2, and define a role for dysferlin in Ca2+-dependent repair of sarcolemmal injury through a process of vesicle fusion. Expression profiling identified a network of genes that are co-regulated in dysferlinopathic mice. Co-immunofluorescence, co-immunoprecipitation, and fluorescence lifetime imaging microscopy revealed that dysferlin normally associates with both annexins A1 and A2 in a Ca2+ and membrane injury-dependent manner. The distribution of the annexins and the efficiency of sarcolemmal wound-healing are significantly disrupted in dysferlin-deficient muscle. We propose a model of muscle membrane healing mediated by dysferlin that is relevant to both normal and dystrophic muscle and defines the annexins as potential muscular dystrophy genes. 相似文献
88.
Esther Kho Lisanne L. de Boer Anouk L. Post Koen K. Van de Vijver Katarzyna J
wiak Henricus J.C.M. Sterenborg Theo J.M. Ruers 《Journal of biophotonics》2019,12(11)
Hyperspectral imaging is a promising technique for resection margin assessment during cancer surgery. Thereby, only a specific amount of the tissue below the resection surface, the clinically defined margin width, should be assessed. Since the imaging depth of hyperspectral imaging varies with wavelength and tissue composition, this can have consequences for the clinical use of hyperspectral imaging as margin assessment technique. In this study, a method was developed that allows for hyperspectral analysis of resection margins in breast cancer. This method uses the spectral slope of the diffuse reflectance spectrum at wavelength regions where the imaging depth in tumor and healthy tissue is equal. Thereby, tumor can be discriminated from healthy breast tissue while imaging up to a similar depth as the required tumor‐free margin width of 2 mm. Applying this method to hyperspectral images acquired during surgery would allow for robust margin assessment of resected specimens. In this paper, we focused on breast cancer, but the same approach can be applied to develop a method for other types of cancer. 相似文献
89.
90.
Wenqing Wang Melanie R. McReynolds Jimmy F. Goncalves Muya Shu Ineke Dhondt Bart P. Braeckman Stephanie E. Lange Kelvin Kho Ariana C. Detwiler Marisa J. Pacella Wendy Hanna-Rose 《The Journal of biological chemistry》2015,290(43):26163-26179
Temporal developmental progression is highly coordinated in Caenorhabditis elegans. However, loss of nicotinamidase PNC-1 activity slows reproductive development, uncoupling it from its typical progression relative to the soma. Using LC/MS we demonstrate that pnc-1 mutants do not salvage the nicotinamide released by NAD+ consumers to resynthesize NAD+, resulting in a reduction in global NAD+ bioavailability. We manipulate NAD+ levels to demonstrate that a minor deficit in NAD+ availability is incompatible with a normal pace of gonad development. The NAD+ deficit compromises NAD+ consumer activity, but we surprisingly found no functional link between consumer activity and reproductive development. As a result we turned to a comparative metabolomics approach to identify the cause of the developmental phenotype. We reveal widespread metabolic perturbations, and using complementary pharmacological and genetic approaches, we demonstrate that a glycolytic block accounts for the slow pace of reproductive development. Interestingly, mitochondria are protected from both the deficiency in NAD+ biosynthesis and the effects of reduced glycolytic output. We suggest that compensatory metabolic processes that maintain mitochondrial activity in the absence of efficient glycolysis are incompatible with the requirements for reproductive development, which requires high levels of cell division. In addition to demonstrating metabolic requirements for reproductive development, this work also has implications for understanding the mechanisms behind therapeutic interventions that target NAD+ salvage biosynthesis for the purposes of inhibiting tumor growth. 相似文献