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81.
Kazuhisa?Nozawa Carlos?A?Casiano John?C?Hamel Christine?Molinaro Marvin?J?Fritzler Edward?KL?ChanEmail author 《Arthritis research & therapy》2002,4(4):R3
Anti-Golgi complex autoantibodies are found primarily in patients with Sjögren's syndrome and systemic lupus erythematosus, although they are not restricted to these diseases. Several Golgi autoantigens have been identified that represent a small family of proteins. Common features of all Golgi autoantigens appear to be their distinct structural organization of multiple α-helical coiled-coil rods in the central domains flanked by non-coiled-coil N-termini and C-termini, and their localization to the cytoplasmic face of Golgi cisternae. Many autoantigens in systemic autoimmune diseases have distinct cleavage products in apoptosis or necrosis and this has raised the possibility that cell death may play a role in the generation of potentially immunostimulatory forms of autoantigens. In the present study, we examined changes in the Golgi complex and associated autoantigens during apoptosis and necrosis. Immunofluorescence analysis showed that the Golgi complex was altered and developed distinctive characteristics during apoptosis and necrosis. In addition, immunoblotting analysis showed the generation of antigenic fragments of each Golgi autoantigen, suggesting that they may play a role in sustaining autoantibody production. Further studies are needed to determine whether the differences observed in the Golgi complex during apoptosis or necrosis may account for the production of anti-Golgi complex autoantibodies. 相似文献
82.
Fraley ME Arrington KL Hambaugh SR Hoffman WF Cunningham AM Young MB Hungate RW Tebben AJ Rutledge RZ Kendall RL Huckle WR McFall RC Coll KE Thomas KA 《Bioorganic & medicinal chemistry letters》2003,13(18):2973-2976
We have discovered 3-(5-thien-3-ylpyridin-3-yl)-1H-indoles as potent inhibitors of KDR kinase activity. This communication details the evolution of this novel class from a potent screening lead of vastly different structure with an emphasis on structural modifications that retained activity and provided improvements in key physical properties. The synthesis and in-depth evaluation of these inhibitors are described. 相似文献
83.
Yamasaki Y Narain S Hernandez L Barker T Ikeda K Segal MS Richards HB Chan EK Reeves WH Satoh M 《Arthritis research & therapy》2006,8(4):R111-10
Replication protein A (RPA), a heterotrimer with subunits of molecular masses 70, 32, and 14 kDa, is a single-stranded-DNA-binding factor involved in DNA replication, repair, and recombination. There have been only three reported cases of anti-RPA in systemic lupus erythematosus (SLE) and Sjögren syndrome (SjS). This study sought to clarify the clinical significance of autoantibodies against RPA. Sera from 1,119 patients enrolled during the period 2000 to 2005 were screened by immunoprecipitation (IP) of 35S-labeled K562 cell extract. Antigen-capture ELISA with anti-RPA32 mAb, immunofluorescent antinuclear antibodies (ANA) and western blot analysis with purified RPA were also performed. Our results show that nine sera immunoprecipitated the RPA70–RPA32–RPA14 complex and all were strongly positive by ELISA (titers 1:62,500 to 1:312,500). No additional sera were positive by ELISA and subsequently confirmed by IP or western blotting. All sera showed fine speckled/homogeneous nuclear staining. Anti-RPA was found in 1.4% (4/276) of SLE and 2.5% (1/40) of SjS sera, but not in rheumatoid arthritis (0/35), systemic sclerosis (0/47), or polymyositis/dermatomyositis (0/43). Eight of nine patients were female and there was no racial predilection. Other positive patients had interstitial lung disease, autoimmune thyroiditis/hepatitis C virus/pernicious anemia, or an unknown diagnosis. Autoantibody specificities found in up to 40% of SLE and other diseases, such as anti-nRNP, anti-Sm, anti-Ro, and anti-La, were unusual in anti-RPA-positive sera. Only one of nine had anti-Ro, and zero of nine had anti-nRNP, anti-Sm, anti-La, or anti-ribosomal P antibodies. In summary, high titers of anti-RPA antibodies were found in nine patients (1.4% of SLE and other diseases). Other autoantibodies found in SLE were rare in this subset, suggesting that patients with anti-RPA may form a unique clinical and immunological subset. 相似文献
84.
85.
We used Pseudomonas aeruginosa, Burkholderia cepacia and Stenotrophomonas maltophilia, live or heat-killed, isolated from the airways of children with Cystic Fibrosis, to stimulate human neutrophils (PMN) and rat alveolar macrophages (AM) to produce reactive oxygen metabolites in the presence or absence of Curosurf, a natural porcine lung surfactant. We determined: (1) the amount of lipid peroxidation (LPO) as assessed by the amounts of malondialdehyde (MDA) and 4-hydroxyalkenals (4-HNE) using the LPO 586 test kit; (2) the production by AM of superoxide with the nitroblue tetrazolium test and (3) of nitric oxide (NO) with the Griess reaction. Stimulation of PMN or AM increases LPO of Curosurf and cell wall lipids. In both types of phagocytes, B. cepacia induced the highest LPO levels followed by P. aeruginosa and S. maltophilia. PMN, stimulated by live bacteria, induced higher LPO than those stimulated by heat-killed bacteria. B. cepacia stimulated AM to produce more superoxide and NO than did P. aeruginosa and S. maltophilia. The high phagocyte-stimulating ability of B. cepacia and its higher surfactant LPO than those of the other bacteria used in this in vitro study may play a role in vivo in the serious clinical condition known as the "Cepacia syndrome". 相似文献
86.
Getting to the fat of the matter: models,methods and assumptions for dealing with lipids in stable isotope analyses 总被引:4,自引:0,他引:4
Within an organism, lipids are depleted in 13C relative to proteins and carbohydrates (more negative δ13C), and variation in lipid content among organisms or among tissue types has the potential to introduce considerable bias into stable isotope analyses that use δ13C. Despite the potential for introduced error, there is no consensus on the need to account for lipids in stable isotope analyses. Here we address two questions: (1) If and when is it important to account for the effects of variation in lipid content on δ13C? (2) If it is important, which method(s) are reliable and robust for dealing with lipid variation? We evaluated the reliability of direct chemical extraction, which physically removes lipids from samples, and mathematical normalization, which uses the carbon-to-nitrogen (C:N) ratio of a sample to normalize δ13C after analysis by measuring the lipid content, the C:N ratio, and the effect of lipid content on δ13C (Δδ13C) of plants and animals with a wide range of lipid contents. For animals, we found strong relationships between C:N and lipid content, between lipid content and Δδ13C, and between C:N and Δδ13C. For plants, C:N was not a good predictor of lipid content or Δδ13C, but we found a strong relationship between carbon content and lipid content, lipid content and Δδ13C, and between and carbon content and Δδ13C. Our results indicate that lipid extraction or normalization is most important when lipid content is variable among consumers of interest or between consumers and end members, and when differences in δ13C between end members is <10–12‰. The vast majority of studies using natural variation in δ13C fall within these criteria. Both direct lipid extraction and mathematical normalization reduce biases in δ13C, but mathematical normalization simplifies sample preparation and better preserves the integrity of samples for δ15N analysis. 相似文献
87.
88.
We have investigated the morphological effects of a genetic locus, Pgm1- t,
that affects the expression of a phosphoglucomutase locus (Pgm1) in liver
of rainbow trout (Salmo gairdneri). We have previously shown that embryos
with liver Pgm1 expression hatch earlier than those without liver Pgm1
expression. We predicted that this difference in developmental rate should
cause a reduction in meristic counts in the more rapidly developing fish
with liver Pgm1 expression. Eight meristic (countable) characters in nine
full-sib groups segregating for the presence or absence of liver Pgm1
expression are in agreement with this prediction. In eight of the nine
families, there is a significant difference in the multivariate
distribution of the eight meristic counts between full sibs with and
without liver Pgm1 expression. This separation in multivariate space is
based on a tendency for lower meristic counts in fish with liver Pgm1
expression. The magnitude of these morphological differences is similar to
that between two subspecies of cutthroat trout (Salmo clarki) that show
substantial genetic divergence at structural loci encoding enzymes (Nei's D
= 0.34). These data support the view that small changes in the
developmental process caused by genetic differences at regulatory genes can
have large effects on morphology.
相似文献
89.
Natural Isolates of Simian Virus 40 from Immunocompromised Monkeys Display Extensive Genetic Heterogeneity: New Implications for Polyomavirus Disease 总被引:6,自引:6,他引:6 下载免费PDF全文
John A. Lednicky Amy S. Arrington A. Renee Stewart Xian Min Dai Connie Wong Sanjeeda Jafar Michael Murphey-Corb Janet S. Butel 《Journal of virology》1998,72(5):3980-3990
Simian virus 40 (SV40) DNAs in brain tissue and peripheral blood mononuclear cells (PBMCs) of eight simian immunodeficiency virus-infected rhesus monkeys with SV40 brain disease were analyzed. We report the detection, cloning, and identification of five new SV40 strains following a quadruple testing-verification strategy. SV40 genomes with archetypal regulatory regions (containing a duplication within the G/C-rich regulatory region segment and a single 72-bp enhancer element) were recovered from seven animal brains, two tissues of which also contained viral genomes with nonarchetypal regulatory regions (containing a duplication within the G/C-rich regulatory region segment as well as a variable duplication within the enhancer region). In contrast, PBMC DNAs from five of six animals had viral genomes with both regulatory region types. It appeared, based on T-antigen variable-region sequences, that nonarchetypal virus variants arose de novo within each animal. The eighth animal exclusively yielded a new type of SV40 strain (SV40-K661), containing a protoarchetypal regulatory region (lacking a duplication within the G/C-rich segment of the regulatory region and containing one 72-bp element in the enhancer region), from both brain tissue and PBMCs. The presence of SV40 in PBMCs suggests that hematogenous spread of viral infection may occur. An archetypal version of a virus similar to SV40 reference strain 776 (a kidney isolate) was recovered from one brain, substantiating the idea that SV40 is neurotropic as well as kidney-tropic. Indirect evidence suggests that maternal-infant transmission of SV40 may have occurred in one animal. These findings provide new insights for human polyomavirus disease. 相似文献
90.
Nikita E. Chavarria Sungmin Hwang Shiyun Cao Xian Fu Mary Holman Dina Elbanna Suzanne Rodriguez Deanna Arrington Markus Englert Sivakumar Uthandi Dieter S?ll Julie A. Maupin-Furlow 《PloS one》2014,9(6)
While cytoplasmic tRNA 2-thiolation protein 1 (Tuc1/Ncs6) and ubiquitin-related modifier-1 (Urm1) are important in the 2-thiolation of 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U) at wobble uridines of tRNAs in eukaryotes, the biocatalytic roles and properties of Ncs6/Tuc1 and its homologs are poorly understood. Here we present the first report of an Ncs6 homolog of archaea (NcsA of Haloferax volcanii) that is essential for maintaining cellular pools of thiolated tRNALysUUU and for growth at high temperature. When purified from Hfx. volcanii, NcsA was found to be modified at Lys204 by isopeptide linkage to polymeric chains of the ubiquitin-fold protein SAMP2. The ubiquitin-activating E1 enzyme homolog of archaea (UbaA) was required for this covalent modification. Non-covalent protein partners that specifically associated with NcsA were also identified including UbaA, SAMP2, proteasome activating nucleotidase (PAN)-A/1, translation elongation factor aEF-1α and a β-CASP ribonuclease homolog of the archaeal cleavage and polyadenylation specificity factor 1 family (aCPSF1). Together, our study reveals that NcsA is essential for growth at high temperature, required for formation of thiolated tRNALysUUU and intimately linked to homologs of ubiquitin-proteasome, translation and RNA processing systems. 相似文献