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251.
Age‐associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis
Jianrui Song Diana Farris Paola Ariza Smriti Moorjani Mita Varghese Muriel Blin Judy Chen Daniel Tyrrell Min Zhang Kanakadurga Singer Morgan Salmon Daniel R. Goldstein 《Aging cell》2023,22(2)
Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro‐atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr −/− recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population. 相似文献
252.
María Isabel Ponferrada-Marín Teresa Roldn-Arjona Rafael R. Ariza 《Nucleic acids research》2009,37(13):4264-4274
Arabidopsis ROS1 belongs to a family of plant 5-methycytosine DNA glycosylases that initiate DNA demethylation through base excision. ROS1 displays the remarkable capacity to excise 5-meC, and to a lesser extent T, while retaining the ability to discriminate effectively against C and U. We found that replacement of the C5-methyl group by halogen substituents greatly decreased excision of the target base. Furthermore, 5-meC was excised more efficiently from mismatches, whereas excision of T only occurred when mispaired with G. These results suggest that ROS1 specificity arises by a combination of selective recognition at the active site and thermodynamic stability of the target base. We also found that ROS1 is a low-turnover catalyst because it binds tightly to the abasic site left after 5-meC removal. This binding leads to a highly distributive behaviour of the enzyme on DNA substrates containing multiple 5-meC residues, and may help to avoid generation of double-strand breaks during processing of bimethylated CG dinucleotides. We conclude that the biochemical properties of ROS1 are consistent with its proposed role in protecting the plant genome from excess methylation. 相似文献
253.
Arfianti Arfianti Athalah Sabillah Sumpena Fauzia Andrini Djojosugito Dita Kartika Sari Ariza Julia Paulina 《Reports of Biochemistry & Molecular Biology》2021,9(4):463
Background:Chronic hepatitis B is a necro-inflammatory of the liver parenchyma caused by hepatitis B virus (HBV) infection leading to liver cirrhosis and hepatocellular carcinoma (HCC). Genetic variants including single nucleotide polymorphisms (SNPs) within genes regulating immune response may contribute to the progression of chronic hepatitis B (CHB) infection. This study aimed to examine the genotype distribution of vitamin D receptor (VDR) polymorphism among patients with CHB infection and to study its association with the development of cirrhosis and hepatoma.Methods:This cross-sectional study analysed 75 CHB patients, consisting of 36 CHB patients without cirrhosis, 25 CHB patients with cirrhosis, and 14 CHB patients with hepatoma. VDR polymorphism was examined using the Amplification Refractory Mutation System Polymerase Chain Reaction (ARMS-PCR) method.Results:Alanine aminotransferase (ALT) and alpha fetoprotein (AFP) levels did not show any significant differences between study groups, but albumin levels in CHB patients with cirrhosis and hepatoma were significantly lower than CHB patients without cirrhosis (p< 0.05). In contrast, the bilirubin levels in CHB patients with cirrhosis was higher than in CHB patients’ cirrhosis. The most common genotypes of VDR polymorphisms were Ff (57.3%), TT (72%), aa (48%) and bb (74.7%) for Fok1, Taq1, Apa1 and Bsm1 respectively. There was no significant different in the genotype distribution of VDR polymorphism between CHB patients without cirrhosis and CHB with cirrhosis or hepatoma. Conclusion:This study suggest that VDR gene polymorphism may not contribute to the progression of CHB infection.Key Words: Cirrhosis, Hepatitis B, Hepatoma, Polymorphism, Vitamin D Receptor 相似文献
254.
Molecular evolution of olfactomedin 总被引:2,自引:0,他引:2
Olfactomedin is a secreted polymeric glycoprotein of unknown function,
originally discovered at the mucociliary surface of the amphibian olfactory
neuroepithelium and subsequently found throughout the mammalian brain. As a
first step toward elucidating the function of olfactomedin, its
phylogenetic history was examined to identify conserved structural motifs.
Such conserved motifs may have functional significance and provide targets
for future mutagenesis studies aimed at establishing the function of this
protein. Previous studies revealed 33% amino acid sequence identity between
rat and frog olfactomedins in their carboxyl terminal segments. Further
analysis, however, reveals more extensive homologies throughout the
molecule. Despite significant sequence divergence, cysteines essential for
homopolymer formation such as the CXC motif near the amino terminus are
conserved, as is the characteristic glycosylation pattern, suggesting that
these posttranslational modifications are essential for function.
Furthermore, evolutionary analysis of a region of 53 amino acids of fish,
frog, rat, mouse, and human olfactomedins indicates that an ancestral
olfactomedin gene arose before the evolution of terrestrial vertebrates and
evolved independently in teleost, amphibian, and mammalian lineages.
Indeed, a distant olfactomedin homolog was identified in Caenorhabditis
elegans. Although the amino acid sequence of this invertebrate protein is
longer and highly divergent compared with its vertebrate homologs, the
protein from C. elegans shows remarkable similarities in terms of conserved
motifs and posttranslational modification sites. Six universally conserved
motifs were identified, and five of these are clustered in the carboxyl
terminal half of the protein. Sequence comparisons indicate that evolution
of the N-terminal half of the molecule involved extensive insertions and
deletions; the C-terminal segment evolved mostly through point mutations,
at least during vertebrate evolution. The widespread occurrence of
olfactomedin among vertebrates and invertebrates underscores the notion
that this protein has a function of universal importance. Furthermore,
extensive modification of its N-terminal half and the acquisition of a
C-terminal SDEL endoplasmic-reticulum- targeting sequence may have enabled
olfactomedin to adopt new functions in the mammalian central nervous
system.
相似文献
255.
256.
Age-associated adipose tissue inflammation promotes monocyte chemotaxis and enhances atherosclerosis
Jianrui Song Diana Farris Paola Ariza Smriti Moorjani Mita Varghese Muriel Blin Judy Chen Daniel Tyrrell Min Zhang Kanakadurga Singer Morgan Salmon Daniel R. Goldstein 《Aging cell》2023,22(2):e13783
Although aging enhances atherosclerosis, we do not know if this occurs via alterations in circulating immune cells, lipid metabolism, vasculature, or adipose tissue. Here, we examined whether aging exerts a direct pro-atherogenic effect on adipose tissue in mice. After demonstrating that aging augmented the inflammatory profile of visceral but not subcutaneous adipose tissue, we transplanted visceral fat from young or aged mice onto the right carotid artery of Ldlr−/− recipients. Aged fat transplants not only increased atherosclerotic plaque size with increased macrophage numbers in the adjacent carotid artery, but also in distal vascular territories, indicating that aging of the adipose tissue enhances atherosclerosis via secreted factors. By depleting macrophages from the visceral fat, we identified that adipose tissue macrophages are major contributors of the secreted factors. To identify these inflammatory factors, we found that aged fat transplants secreted increased levels of the inflammatory mediators TNFα, CXCL2, and CCL2, which synergized to promote monocyte chemotaxis. Importantly, the combined blockade of these inflammatory mediators impeded the ability of aged fat transplants to enhance atherosclerosis. In conclusion, our study reveals that aging enhances atherosclerosis via increased inflammation of visceral fat. Our study suggests that future therapies targeting the visceral fat may reduce atherosclerosis disease burden in the expanding older population. 相似文献
257.
María Isabel Ponferrada-Marín Teresa Roldán-Arjona Rafael R. Ariza 《Nucleic acids research》2012,40(22):11554-11562
Active DNA demethylation processes play a critical role in shaping methylation patterns, yet our understanding of the mechanisms involved is still fragmented and incomplete. REPRESSOR OF SILENCING 1 (ROS1) is a prototype member of a family of plant 5-methylcytosine DNA glycosylases that initiate active DNA demethylation through a base excision repair pathway. As ROS1 binds DNA non-specifically, we have critically tested the hypothesis that facilitated diffusion along DNA may contribute to target location by the enzyme. We have found that dissociation of ROS1 from DNA is severely restricted when access to both ends is obstructed by tetraloops obstacles. Unblocking any end facilitates protein dissociation, suggesting that random surface sliding is the main route to a specific target site. We also found that removal of the basic N-terminal domain of ROS1 significantly impairs the sliding capacity of the protein. Finally, we show that sliding increases the catalytic efficiency of ROS1 on 5-meC:G pairs, but not on T:G mispairs, thus suggesting that the enzyme achieves recognition and excision of its two substrate bases by different means. A model is proposed to explain how ROS1 finds its potential targets on DNA. 相似文献
258.
C-banding has been performed on Dictyocaulus filaria using both original and modified techniques. The karyotype is reported based on C band observations. The existence of large heterochromatic blocks appears to be the cause of the low chiasmata frequency. 相似文献
259.
The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus 总被引:1,自引:0,他引:1
Padgett RW; Loeb DD; Snyder LR; Edgell MH; Hutchison CA d 《Molecular biology and evolution》1987,4(1):30-45
Recombinant DNA clones have been isolated that contain 80 kb of the
beta-globin complex from the deer mouse, Peromyscus maniculatus.
Comparisons of this complex with that from the laboratory mouse, Mus
domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3,
Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin
complex since the two species diverged. Unlike other mammals studied thus
far, the deer mouse possesses three adult genes. Partial sequence analysis
indicates that each of the three adult genes is intact and hence may be
functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to
genomic blots from Peromyscus reveals that it has a homologous counterpart
in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO
and Hbb-bhl, are also found in Peromyscus. The strong hybridization between
the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO
genes suggest that both pairs are important for the ontogeny of these mice
although no known product has been identified for the Hbb-bhO genes. The
presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication
that created this related gene set occurred before the two lineages
diverged. A single gene for Hbb-y has been isolated from Peromyscus. The
adult region in Peromyscus has undergone significant divergence from the
same region in Mus, having three rather than two adult genes, the
acquisition of at least 15 kb of extra DNA relative to Mus, and possibly
the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in
contrast, contains the same set of genes apparently distributed over the
same amount of DNA as in the Mus beta- globin complex. This observation
suggests that the embryonic region of the complex is more evolutionarily
stable than the adult region.
相似文献
260.