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81.
Yang N Li H Criswell LA Gregersen PK Alarcon-Riquelme ME Kittles R Shigeta R Silva G Patel PI Belmont JW Seldin MF 《Human genetics》2005,118(3-4):382-392
We and others have identified several hundred ancestry informative markers (AIMs) with large allele frequency differences between different major ancestral groups. For this study, a panel of 199 widely distributed AIMs was used to examine a diverse set of 796 DNA samples including self-identified European Americans, West Africans, East Asians, Amerindians, African Americans, Mexicans, Mexican Americans, Puerto Ricans and South Asians. Analysis using a Bayesian clustering algorithm (STRUCTURE) showed grouping of individuals with similar ethnic identity without any identifier other than the AIMs genotyping and showed admixture proportions that clearly distinguished different individuals of mixed ancestry. Additional analyses showed that, for the majority of samples, the predicted ethnic identity corresponded with the self-identified ethnicity at high probability (P > 0.99). Overall, the study demonstrates that AIMs can provide a useful adjunct to forensic medicine, pharmacogenomics and disease studies in which major ancestry or ethnic affiliation might be linked to specific outcomes.Electronic Supplementary Material Supplementary material is available for this article at 相似文献
82.
Thomas J. Corydon Mette Wilsbech Cathrine Jespersgaard Brage S. Andresen Anders D. Børglum Søren Pedersen Lars Bolund Niels Gregersen Peter Bross 《Mammalian genome》2000,11(10):899-905
We have determined the cDNA sequence and exon/intron structure of the human CLPX gene encoding a human ortholog of the E. coli ClpX chaperone and protease subunit. The CLPX gene comprises 14 exons and encodes a 633-amino acid-long precursor polypeptide.
The polypeptide contains an N-terminal putative mitochondrial transit peptide, and expression of a full-length ClpX cDNA tagged
at its C-terminus (Myc-His) shows that the polypeptide is transported into mitochondria. FISH analysis localized the CLPX
gene to human Chromosome (Chr) 15q22.1-22.32. This localization was refined by radiation hybrid mapping placing the CLPX gene
4.6 cR distal to D15S159. Murine ClpX cDNA was sequenced, and the mouse Clpx locus was mapped to a position between 31 and 42 cM offset from the centromere on mouse Chr 9. Experimental observations
indicate the presence of a pseudogene in the mouse genome and sequence variability between mouse ClpX cDNAs from different
strains. Alignment of the human and mouse ClpX amino acid sequences with ClpX sequences from other organisms shows that they
display the typical modular organization of domains with one AAA+ domain common to a large group of ATPases and several other domains conserved in ClpX orthologs linked by non-conserved sequences.
Notably, a C-4 zinc finger type motif is recognized in human and mouse ClpX. This motif of so far unknown function is present
only in a subset of the known ClpX sequences.
Received: 5 April 2000 / Accepted: 14 June 2000 相似文献
83.
Brage S. Andresen Thomas J. Corydon Mette Wilsbech Peter Bross Lisbeth D. Schroeder Tina F. Hindkjær Lars Bolund Niels Gregersen 《Mammalian genome》2000,11(4):275-280
Mutations that cause accumulation or rapid degradation owing to protein misfolding are a frequent cause of inherited disease
in humans. In Escherichia coli, Clpp protease is one of the components of the protein quality control system that handles misfolded proteins. In the present
study, we have characterized the mouse Clpp cDNA sequence, the organization of the mouse gene, the chromosomal localization,
and the tissue-specific expression pattern. Moreover, the cellular localization and processing of mouse Clpp was studied by
overexpression in transfected eukaryotic cells. Our results indicate that mouse and human Clpp have similar roles, and they
provide the molecular basis for establishing a Clpp knockout mouse and to study its phenotype, thereby shedding light on a possible role of Clpp in human disease.
Received: 25 June 1999 / Accepted: 9 December 1999 相似文献
84.
Plant senescence and crop productivity 总被引:3,自引:0,他引:3
Per L. Gregersen Andrea Culetic Luca Boschian Karin Krupinska 《Plant molecular biology》2013,82(6):603-622
85.
Stephan Otto Birger Mensel Nele Friedrich Sophia Sch?fer Christoph Mahlke Wolfram von Bernstorff Karen Bock Norbert Hosten Jens-Peter Kühn 《PloS one》2015,10(4)
Purpose
To investigate predictors of technical success and complications of computed tomography (CT)-guided percutaneous transthoracic needle biopsy of potentially malignant pulmonary tumors.Material and Methods
From 2008 to 2009, technical success and rate of complications of CT-guided percutaneous transthoracic lung needle biopsies of patients with suspicious pulmonary tumors were retrospectively evaluated. The influence on technical success and rate of complications was assessed for intervention-related predictors (lesion diameter, length of biopsy pathway, number of pleural transgressions, and needle size) and patient-related predictors (age, gender, reduced lung function). In addition, technical success and rate of complications were compared between different interventional radiologists.Results
One hundred thirty-eight patients underwent biopsies by 15 interventional radiologists. The overall technical success rate was 84.1% and was significantly different between interventional radiologists (range 25%-100%; p<0.01). Intervention-related and patient-related predictors did not influence the technical success rate. The overall complication rate was 59.4% with 39.1% minor complications and 21.0% major complications. The rate of complications was influenced by lesion diameter and distance of biopsy pathway. Interventional radiologist-related rates of complications were not statistically different.Conclusions
Technical success of percutaneous, transthoracic lung needle biopsies of pulmonary tumors is probably dependent on the interventional radiologist. In addition, lesion diameter and length of biopsy pathway are predictors of the rate of complications. 相似文献86.
87.
Bie AS Palmfeldt J Hansen J Christensen R Gregersen N Corydon TJ Bross P 《Cell stress & chaperones》2011,16(6):633-640
Mitochondrial dysfunction is associated with neurodegenerative diseases and mutations in the HSPD1 gene, encoding the mitochondrial Hsp60 chaperone, are the causative factors of two neurodegenerative diseases, hereditary
spastic paraplegia and MitChap60 disease. In cooperation with Hsp10, Hsp60 forms a barrel-shaped complex, which encloses unfolded
polypeptides and provides an environment facilitating folding. We have generated an Hsp60 variant with a mutation (Asp423Ala)
in the ATPase domain and established a stable human embryonic kidney (HEK293) cell line allowing tetracycline-controlled expression
of this mutant variant. We monitored expression of the Hsp60–Asp423Ala variant protein following induction and examined its
effects on cellular properties. We showed that the folding of mitochondrial-targeted green fluorescent protein, a well-known
substrate protein of Hsp60, was consistently impaired in cells expressing Hsp60–Asp423Ala. The level of the Hsp60–Asp423Ala
variant protein increased over time upon induction, cell proliferation stopped after 48-h induction and mitochondrial membrane
potential decreased in a time-dependent manner. In summary, we have established a stable cell line with controllable expression
of an Hsp60 variant, which allows detailed studies of different degrees of Hsp60 deficiency. 相似文献
88.
Wang N Shen N Vyse TJ Anand V Gunnarson I Sturfelt G Rantapää-Dahlqvist S Elvin K Truedsson L Andersson BA Dahle C Ortqvist E Gregersen PK Behrens TW Hammarström L 《Molecular medicine (Cambridge, Mass.)》2011,17(11-12):1383-1396
Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) on the basis of both our own recent large-scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune disorders, including GD, SLE, T1D, CD, MG and RA, and a strong association with the major histocompatibility complex (MHC) region has been reported. In addition, non-MHC genes, such as interferon-induced helicase 1 (IFIH1) and c-type lectin domain family 16, member A (CLEC16A), are also associated with the development of IgAD and some of the above diseases. This indicates a possible common genetic background. In this review, we present suggestive evidence for a shared genetic predisposition between these disorders. 相似文献
89.
Chung SA Taylor KE Graham RR Nititham J Lee AT Ortmann WA Jacob CO Alarcón-Riquelme ME Tsao BP Harley JB Gaffney PM Moser KL;SLEGEN Petri M Demirci FY Kamboh MI Manzi S Gregersen PK Langefeld CD Behrens TW Criswell LA 《PLoS genetics》2011,7(3):e1001323
Systemic lupus erythematosus (SLE) is a clinically heterogeneous, systemic autoimmune disease characterized by autoantibody formation. Previously published genome-wide association studies (GWAS) have investigated SLE as a single phenotype. Therefore, we conducted a GWAS to identify genetic factors associated with anti–dsDNA autoantibody production, a SLE–related autoantibody with diagnostic and clinical importance. Using two independent datasets, over 400,000 single nucleotide polymorphisms (SNPs) were studied in a total of 1,717 SLE cases and 4,813 healthy controls. Anti–dsDNA autoantibody positive (anti–dsDNA +, n = 811) and anti–dsDNA autoantibody negative (anti–dsDNA –, n = 906) SLE cases were compared to healthy controls and to each other to identify SNPs associated specifically with these SLE subtypes. SNPs in the previously identified SLE susceptibility loci STAT4, IRF5, ITGAM, and the major histocompatibility complex were strongly associated with anti–dsDNA + SLE. Far fewer and weaker associations were observed for anti–dsDNA – SLE. For example, rs7574865 in STAT4 had an OR for anti–dsDNA + SLE of 1.77 (95% CI 1.57–1.99, p = 2.0E-20) compared to an OR for anti–dsDNA – SLE of 1.26 (95% CI 1.12–1.41, p = 2.4E-04), with pheterogeneity<0.0005. SNPs in the SLE susceptibility loci BANK1, KIAA1542, and UBE2L3 showed evidence of association with anti–dsDNA + SLE and were not associated with anti–dsDNA – SLE. In conclusion, we identified differential genetic associations with SLE based on anti–dsDNA autoantibody production. Many previously identified SLE susceptibility loci may confer disease risk through their role in autoantibody production and be more accurately described as autoantibody propensity loci. Lack of strong SNP associations may suggest that other types of genetic variation or non-genetic factors such as environmental exposures have a greater impact on susceptibility to anti–dsDNA – SLE. 相似文献
90.
Liu M Rogers L Cheng Q Shao Y Fernandez-Beros ME Hirschhorn JN Lyon HN Gajdos ZK Vedantam S Gregersen P Seldin MF Bleck B Ramasamy A Hartikainen AL Jarvelin MR Kuokkanen M Laitinen T Eriksson J Lehtimäki T Raitakari OT Reibman J 《PloS one》2011,6(9):e25099