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A recent high-density linkage screen confirmed that the HLA complex contains the strongest genetic factor for the risk of multiple sclerosis (MS). In parallel, a linkage disequilibrium analysis using 650 single nucleotide polymorphisms (SNP) markers of the HLA complex mapped the entire genetic effect to the HLA-DR-DQ subregion, reflected by the well-established risk haplotype HLA-DRB1*15,DQB1*06. Contrary to this, in a cohort of 1,084 MS patients and 1,347 controls, we show that the HLA-A gene confers an HLA-DRB1 independent influence on the risk of MS (P = 8.4x10(-10)). This supports the opposing view, that genes in the HLA class I region indeed exert an additional influence on the risk of MS, and confirms that the class I allele HLA-A*02 is negatively associated with the risk of MS (OR = 0.63, P = 7x10(-12)) not explained by linkage disequilibrium with class II. The combination of HLA-A and HLA-DRB1 alleles, as represented by HLA-A*02 and HLA-DRB1*15, was found to influence the risk of MS 23-fold. These findings imply complex autoimmune mechanisms involving both the regulatory and the effector arms of the immune system in the triggering of MS. 相似文献
54.
Boel Lanne Jeana Cîopraga Jörgen Bergström Cecilia Motas Karl-Anders Karlsson 《Glycoconjugate journal》1994,11(4):292-298
The carbohydrate-binding specificity ofPseudomonas aeruginosa lectin I (PA-I) in iodinated or biotinylated form was studied. A large number of glycosphingolipids, as well as some glycoproteins and neoglycoproteins were used as ligands. Also, inhibition by free saccharides of PA-I binding to glycosphingolipids was tested. It was found that the lectin binds most strongly to terminal and nonsubstituted Gal3Gal- or Gal4Gal-structures.Abbreviations PA-I
Pseudomonas aeruginosa lectin I
- Cer
ceramide
- lactosylceramide
Gal4GlcCer
- iso globotriaosylcerami
Gal3Gal4GlcCer
- globotriaosylceramide
Gal4Gal4GlcCer
- globoside or globotetraosylceramide
GalNAc3Gal4Gal4GlcCer
- Forssman glycolipid
GalNAc3GalNAc3Gal4Gal4GlcCer
- P1 glycolipid
Gal4Gal4GlcNAc3Gal4GlcCer
- lactoneotetraosylceramide
Gal4GlcNAc3Gal4GlcCer
- B5 glycolipid
Gal3Gal4GlcNAc3Gal4GlcCer
- gangliotetraosylceramide
Gal3GalNAc4Gal4GlcCer
- GM1
Gal3GalNAc4(NeuAc3)Gal4GlcCer
- RBC
red blood cells
- BSA
bovine serum albumin
- PBS
phosphate-buffered saline
- SDS
sodium dodecyl sulfate
- TLC
thin-layer chromatography
- HPLC
high pressure liquid chromatography
- MS
mass spectrometry
- FAB
fast-atom bombardment
- EI
electron impact 相似文献
55.
Growth stimulatory angiotensin II type-1 receptor is upregulated in breast hyperplasia and in situ carcinoma but not in invasive carcinoma 总被引:4,自引:1,他引:4
Boel De Paepe Valerie L. Verstraeten Christian R. De Potter Luc A. Vakaet Gillian R. Bullock 《Histochemistry and cell biology》2001,116(3):247-254
Two different receptors which bind angiotensin II specifically have been identified in humans and were designated angiotensin II type-1 receptor (AT1) and angiotensin II type-2 receptor (AT2). They only have 34% sequence homology and act through different signalling pathways. AT1 stimulation has been implicated in hypertrophy and hyperplasia in various tissues. In order to study the involvement of AT1 in tissues from controls (n=10) and patients with hyperplasia (n=33), ductal carcinoma in situ (DCIS) (n=23) and invasive carcinoma of the breast (n=25), we tested biopsies and breast-derived cell lines using immunocytochemistry, in situ hybridisation and cell proliferation techniques. The results show specific overexpression of AT1 receptor on the cytoplasmic membrane of cells of hyperplastic lesions with and without atypia and on DCIS of the breast. Evidence for growth stimulation is provided by in vitro experiments showing growth induction by angiotensin II of T47D cells which express the AT1 but not the AT2 receptor. The expression of AT1 on the cell membrane disappears in invasive breast cancer cells suggesting a regulatory pathway which is no longer needed in invasive carcinoma. The specific AT1 expression upregulation might well be an important step in the pathogenesis of hyperplasia of the breast, which is regarded as a precursor lesion for breast cancer. 相似文献
56.
Spring wheat (Triticum aestivum L.) and pea (Pisum spp.) genotypes were tested for reaction to root inoculation with rhizosphere bacteria affecting plant growth. Plant response was studied in greenhouse experiments after treatment of seedlings with bacteria suspended in nutrient broth. Significant genotype variation was found in both wheat and pea in terms of shoot dry weight and severity of bacteria-induced leaf symptoms. For most bacterial isolates tested, there was good correlation between ratings of leaf symptoms 7 to 14 days after inoculation and growth inhibition measured after four weeks. Interactions between isolates and plant genotypes were significant in both wheat and pea (P=0.0024 and 0.0001, respectively), but genotypes with sensitivity or tolerance to most isolates could be distinguished. In an outdoor pot experiment, two of the bacterial isolates caused delayed plant development and differential decreases in grain yield of wheat genotypes. The hypothesis that the reaction of wheat genotypes to the tested becteria was related to their influence on bacterial establishment in the rhizosphere could not be substantiated. 相似文献
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Keld Kaltoft Susanne Bisballe Thomas Dyrberg Esper Boel Poul Baad Rasmussen Kristian Thestrup-Pedersen 《In vitro cellular & developmental biology. Animal》1992,28(3):161-167
Summary From a plaque biopsy of a patient with mycosis fungoides, two different continuous cell lines were established by including
both IL-2 and IL-4 in culture medium. Both continuous cell lines appeared with characteristic chromosome markers after approximately
40 cell population doublings. The initial karyotype recognized in T cells from the skin biopsy was 46,XY and the karyotypes
of the continuous cell strains were 46,XY, -18, + i(18q) and another with multiple chromosome aberrations as described in
Sezary T-cell leukemia. Phenotyping with monoclonal antibodies and T-cell receptor analysis indicates that the latter cell
strain represents a minority of T-cells in the plaque. Due to its many chromosomal aberrations it probably represents the
malignant cell, which may be a central cell in the immune stimulation taking place in the skin. 相似文献
60.
The family of adenosine deaminases acting on RNA (ADARs) targets adenosines in RNA that is mainly double stranded. Some substrates are promiscuously deaminated whereas others, such as the mammalian glutamate receptor B (gluR-B) pre-mRNA, are more selectively deaminated. Many DNA/RNA-base modification enzymes use a base flipping mechanism to be able to reach their target base and it is believed that ADARs function in a similar way. In this study we used molecular dynamics (MD) simulations to describe two sites on the gluR-B pre-mRNA, the selectively targeted R/G site and the nontargeted 46 site, in an attempt to explain the substrate specificity. We used regular MD and also a forced base flipping method with umbrella sampling to calculate the free energy of base opening. Spontaneous opening of the mismatched adenosine was observed for the R/G site but not for the 46 site. 相似文献