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141.
Seno T Hamaguchi M Ashihara E Kohno M Ishino H Yamamoto A Kadoya M Nakamura K Murakami K Matoba S Maekawa T Kawahito Y 《PloS one》2011,6(10):e25541
Aim
15-Deoxy-Δ12,14 Prostaglandin J2 (15d-PGJ2) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ2 can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ2.Methods
We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ2 intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion.Results
Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ2, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ2 treated mice. The 15d-PGJ2 also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions.Conclusion
This is the first report 15d-PGJ2, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ2 may be a beneficial therapeutic agent for atherosclerosis. 相似文献142.
143.
Nagai Y Nochi T Watanabe K Watanabe K Aso H Kitazawa H Matsuzaki M Ohwada S Yamaguchi T 《Cell and tissue research》2005,322(3):455-462
A pro-inflammatory cytokine, interleukin 18 (IL-18), induces intracellular expression of IL-1 and the release of IL-6. IL-1
and IL-6 has been detected in anterior pituitary cells, suggesting that IL-18 is produced in anterior pituitary cells and
may serve to aid immuno-endocrine regulation. In the present study, we addressed this hypothesis by investigating the intracellular
localization of IL-18 and its receptor in bovine anterior pituitary gland. IL-18 mRNA and its protein were detected in the
anterior pituitary gland by RT-PCR and Western blotting. In situ hybridization showed that IL-18 mRNA was expressed in the
anterior pituitary cells. Immunohistochemistry of IL-18 and specific hormones revealed the presence of IL-18 in somatotrophs.
Furthermore, the expression of GH mRNA in IL-18 immunoreactive cells was confirmed by immuno-laser microdissection. These
results first demonstrated that somatotrophs produced IL-18. Subsequently, the distribution of the IL-18 receptor alpha (IL-18Rα)
was investigated in order to understand IL-18 signaling among the anterior pituitary cells. Bovine IL-18Rα cDNA was partially
sequenced and detected in the anterior pituitary gland by RT-PCR. Immunohistochemistry of IL-18Rα, IL-18 and GH showed that
IL-18Rα was co-localized in IL-18 immunoreactive cells or somatotrophs. These data suggest that IL-18 acts on somatotrophs
as an immuno-endocrine mediator through the autocrine pathway.
This work was supported by a Grant-in-Aid for Scientific Research (B) (No.13460122) from the Ministry of Education, Science
and Culture of Japan 相似文献
144.
145.
A simple method for predicting the functional differentiation of duplicate genes and its application to MIKC-type MADS-box genes 总被引:1,自引:0,他引:1 下载免费PDF全文
A simple statistical method for predicting the functional differentiation of duplicate genes was developed. This method is based on the premise that the extent of functional differentiation between duplicate genes is reflected in the difference in evolutionary rate because the functional change of genes is often caused by relaxation or intensification of functional constraints. With this idea in mind, we developed a window analysis of protein sequences to identify the protein regions in which the significant rate difference exists. We applied this method to MIKC-type MADS-box proteins that control flower development in plants. We examined 23 pairs of sequences of floral MADS-box proteins from petunia and found that the rate differences for 14 pairs are significant. The significant rate differences were observed mostly in the K domain, which is important for dimerization between MADS-box proteins. These results indicate that our statistical method may be useful for predicting protein regions that are likely to be functionally differentiated. These regions may be chosen for further experimental studies. 相似文献
146.
Selectionism and neutralism in molecular evolution 总被引:20,自引:0,他引:20
Nei M 《Molecular biology and evolution》2005,22(12):2318-2342
Charles Darwin proposed that evolution occurs primarily by natural selection, but this view has been controversial from the beginning. Two of the major opposing views have been mutationism and neutralism. Early molecular studies suggested that most amino acid substitutions in proteins are neutral or nearly neutral and the functional change of proteins occurs by a few key amino acid substitutions. This suggestion generated an intense controversy over selectionism and neutralism. This controversy is partially caused by Kimura's definition of neutrality, which was too strict (|2Ns|< or =1). If we define neutral mutations as the mutations that do not change the function of gene products appreciably, many controversies disappear because slightly deleterious and slightly advantageous mutations are engulfed by neutral mutations. The ratio of the rate of nonsynonymous nucleotide substitution to that of synonymous substitution is a useful quantity to study positive Darwinian selection operating at highly variable genetic loci, but it does not necessarily detect adaptively important codons. Previously, multigene families were thought to evolve following the model of concerted evolution, but new evidence indicates that most of them evolve by a birth-and-death process of duplicate genes. It is now clear that most phenotypic characters or genetic systems such as the adaptive immune system in vertebrates are controlled by the interaction of a number of multigene families, which are often evolutionarily related and are subject to birth-and-death evolution. Therefore, it is important to study the mechanisms of gene family interaction for understanding phenotypic evolution. Because gene duplication occurs more or less at random, phenotypic evolution contains some fortuitous elements, though the environmental factors also play an important role. The randomness of phenotypic evolution is qualitatively different from allele frequency changes by random genetic drift. However, there is some similarity between phenotypic and molecular evolution with respect to functional or environmental constraints and evolutionary rate. It appears that mutation (including gene duplication and other DNA changes) is the driving force of evolution at both the genic and the phenotypic levels. 相似文献
147.
Nakamiya K Hashimoto S Ito H Edmonds JS Morita M 《Applied and environmental microbiology》2005,71(3):1254-1258
By using 1,4-dioxane as the sole source of carbon, a 1,4-dioxane-degrading microorganism was isolated from soil. The fungus, termed strain A, was able to utilize 1,4-dioxane and many kinds of cyclic ethers as the sole source of carbon and was identified as Cordyceps sinensis from its 18S rRNA gene sequence. Ethylene glycol was identified as a degradation product of 1,4-dioxane by the use of deuterated 1,4-dioxane-d8 and gas chromatography-mass spectrometry analysis. A degradation pathway involving ethylene glycol, glycolic acid, and oxalic acid was proposed, followed by incorporation of the glycolic acid and/or oxalic acid via glyoxylic acid into the tricarboxylic acid cycle. 相似文献
148.
Regulation of p53 translation and induction after DNA damage by ribosomal protein L26 and nucleolin 总被引:15,自引:0,他引:15
Increases in p53 protein levels after DNA damage have largely been attributed to an increase in the half-life of p53 protein. Here we demonstrate that increased translation of p53 mRNA is also a critical step in the induction of p53 protein in irradiated cells. Ribosomal protein L26 (RPL26) and nucleolin were found to bind to the 5' untranslated region (UTR) of p53 mRNA and to control p53 translation and induction after DNA damage. RPL26 preferentially binds to the 5'UTR after DNA damage, and its overexpression enhances association of p53 mRNA with heavier polysomes, increases the rate of p53 translation, induces G1 cell-cycle arrest, and augments irradiation-induced apoptosis. Opposite effects were seen when RPL26 expression was inhibited. In contrast, nucleolin overexpression suppresses p53 translation and induction after DNA damage, whereas nucleolin downregulation promotes p53 expression. These findings demonstrate the importance of increased translation of p53 in DNA-damage responses and suggest critical roles for RPL26 and nucleolin in affecting p53 induction. 相似文献
149.
150.