全文获取类型
收费全文 | 2124篇 |
免费 | 88篇 |
出版年
2024年 | 2篇 |
2023年 | 9篇 |
2022年 | 29篇 |
2021年 | 48篇 |
2020年 | 27篇 |
2019年 | 51篇 |
2018年 | 57篇 |
2017年 | 36篇 |
2016年 | 86篇 |
2015年 | 118篇 |
2014年 | 124篇 |
2013年 | 157篇 |
2012年 | 214篇 |
2011年 | 204篇 |
2010年 | 130篇 |
2009年 | 106篇 |
2008年 | 161篇 |
2007年 | 144篇 |
2006年 | 88篇 |
2005年 | 93篇 |
2004年 | 78篇 |
2003年 | 65篇 |
2002年 | 42篇 |
2001年 | 28篇 |
2000年 | 29篇 |
1999年 | 25篇 |
1998年 | 7篇 |
1997年 | 5篇 |
1996年 | 1篇 |
1995年 | 3篇 |
1994年 | 1篇 |
1993年 | 5篇 |
1992年 | 9篇 |
1991年 | 4篇 |
1989年 | 3篇 |
1988年 | 1篇 |
1986年 | 3篇 |
1985年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1976年 | 2篇 |
1975年 | 2篇 |
1973年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 3篇 |
1965年 | 1篇 |
排序方式: 共有2212条查询结果,搜索用时 15 毫秒
951.
Kim JM Lim BK Ho SH Yun SH Shin JO Park EM Kim DK Kim S Jeon ES 《Biochemical and biophysical research communications》2006,344(3):765-771
Tumor necrosis factor-alpha (TNF-alpha) is one of the major cytokines that modulate the immune response in viral myocarditis, but its role has not yet been thoroughly evaluated. We antagonized TNF-alpha using the expressed soluble p75 TNF receptor linked to the Fc portion of the human IgG1 gene (sTNFR:Fc) by in vivo electroporation, and evaluated its effects on experimental coxsackieviral B3 (CVB3) myocarditis. A plasmid DNA encoding sTNFR:Fc (15microg/mouse) was injected into the gastrocnemius muscles of Balb/C male mice followed by electroporation (day -1). Control mice were injected with an empty vector. One day after electroporation, mice were infected with CVB3 (day 0). Serum levels of sTNFR:Fc increased from day 2 and peaked at day 5 following electroporation. The heart virus titers of sTNFR:Fc mice were higher than those of controls at day 3. However, subsequent to day 12, the survival rates of the sTNFR:Fc mice were significantly higher than those of the controls (36% versus 0% at day 27, P<0.01). Histopathological examination indicated that inflammation and myocardial fibrosis were significantly decreased in sTNFR:Fc mice at day 12. The expressed sTNFR:Fc could modulate the inflammatory process during the post-viremic phase of viral myocarditis. 相似文献
952.
Oh JH Jeon YJ Jeong SY Hong SM Lee JS Nho SK Kang SW Kim NS 《Biochemical and biophysical research communications》2006,343(3):864-872
To elucidate the molecular mechanisms associated with metamorphic phenomenon relating to Bombyx mori, an important organism in the sericulture industry, we identified genes that are expressed in the different developmental stages, specifically the embryonic (ES) and larval (LS) stages of B. mori. Of 8230 high-quality ESTs from two full-length enriched cDNA libraries, 3442 of the ES ESTs were coalesced into 1325 clusters, while 4788 were coalesced into 927 clusters. The functional classification of these ESTs based on Gene Ontology showed that the types of genes that are associated with oxidoreductase activity, enzyme inhibition, and larval development were highly observed in LS, whereas the types of genes that are involved in nucleotide binding, enzyme activity, and protein transport activity were highly observed in ES. In addition, when the gene expression profile between ES and LS was examined by counting the EST frequencies in each library, 69 genes were identified as being either up- or down-regulated in the larval stage compared to the embryonic stage (P>0.99) and this was confirmed by semi-quantitative RT-PCR. The results show that genes involved in proteolysis and peptidolysis, and lipid and carbohydrate metabolism were dramatically up-regulated in LS, while those related to protein metabolism, DNA/RNA, and coenzymes were highly down-expressed. In particular, a GO analysis of these genes revealed that genes that are involved in hydrolase activity were observed to be highly expressed in amount as well as diversity in LS, while those involved in nucleic acid binding were highly expressed in ES. These data may contribute to elucidating genetic events that distinguish the developmental stage and to our understanding of the metamorphosis of B. mori. 相似文献
953.
Induction of Transcription Factor A-myb Expression in Reactive Astrocytes Following an Excitotoxic Lesion in the Mouse Hippocampus 总被引:1,自引:1,他引:0
Jeon GS Byun HJ Park SK Park SW Kim DW Seo JH Cha CI Cho SS 《Neurochemical research》2006,31(11):1371-1374
In the present study, we examined patterns of A-myb expression in the kainic acid (KA)-treated mouse hippocampus. Western blot analysis revealed that A-myb expression was dramatically increased in brain 3 days after KA treatment, and was sustained for more than 7 days. A-myb immunoreactivity was restricted to hippocampal neurons in control mice. Three days after KA treatment, strong A-myb immunoreactivity was observed in reactive astrocytes throughout the CA3 region. Thereafter, A-myb immunoreactive astrocytes gradually concentrated around the CA3 region in parallel with selective neuronal loss, and only a few A-myb immunoreactive astrocytes persisted in the CA3 region 14 days after KA treatment. These findings suggest that the A-myb plays a role in the reactive gliosis signaling pathway in KA-induced excitotoxic lesions. 相似文献
954.
Son YO Choi KC Lee JC Kook SH Lee HJ Jeon YM Kim JG Kim J Lee WK Jang YS 《Journal of cellular biochemistry》2006,99(5):1420-1430
Epstein-Barr virus (EBV) infects more than 90% of the human population and has a potential oncogenic nature. Trichostatin A (TSA) has potent antitumor activity, but its exact mechanism on EBV-infected cells is unclear. This study examined the effects of TSA on proliferation and apoptosis of the Burkitt's lymphoma cell line, Akata. TSA treatment inhibited cell growth and induced cytotoxicity in both the EBV-negative and -positive Akata cells. TSA sensitively induced apoptosis in both cells, as demonstrated by the increased number of positively stained cells in the TUNEL assay, the migration of many cells to sub-G1 phase by flow cytometric analysis, and the formation of DNA ladders. This suggests that EBV has no effect on the sensitivity to TSA. Western blot analysis showed that the cleavage of PARP and Bid and the activation of caspases are closely related to the TSA-induced apoptosis of the cells. The reduction in mitochondrial transition potential and the release of apoptosis-inducing factor from mitochondria to cytosol was also observed after the TSA treatment, but was suppressed by treating the cells with a cathepsin B inhibitor. Overall, these findings suggest that besides the caspase-dependent pathway, mitochondrial events are also associated with the TSA-induced apoptosis of Akata cells. 相似文献
955.
956.
Lee HS Kim YJ Bae SS Jeon JH Lim JK Jeong BC Kang SG Lee JH 《Marine biotechnology (New York, N.Y.)》2006,8(4):425-432
Genomic analysis of a hyperthermophilic archaeon Thermococcus sp. NA1 revealed the presence of an 885-bp open reading frame encoding a protein of 295 amino acids with a calculated molecular
mass of 32,981 Da. Analysis of the deduced amino acid sequence showed that amino acid residues important for catalytic activity
and the metal binding ligands conserved in all of methionyl aminopeptidases (MetAP) were also conserved and belonged to type
IIa MetAP. The protein, designated TNA1_MetAP (Thermococcus sp. NA1 MetAP), was cloned and expressed in Escherichia coli. The recombinant enzyme was a Mn2+-, Ni2+-, Fe2+-, or Co2+-dependent metallopeptidase. Optimal MetAP activity against l-methionine p-nitroanilide (Met-pNA) (K
m = 0.68 mM) occurred at pH 7.0 and 80 to 90°C. The MetAP was very unstable compared to Pyrococcus furiosus MetAP, which was completely inactivated by heating at 80°C for 5 min. It seemed likely that the cysteine residue (Cys53)
played a critical role in regulating the thermostability of TNA1_MetAP. 相似文献
957.
958.
Doh KO Park JO Kim YW Park SY Jeong JH Jeon JR Lee SK Kim JY 《Physiological research / Academia Scientiarum Bohemoslovaca》2006,55(4):413-419
We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring glucose transport. Male Wistar rats were fed rat chow or high-fat diets for 30 days. Before sacrifice, rats fed high-fat diet were subcutaneously injected with leptin (1 mg/kg b.w.) for 3 days. The glucose transport in epitrochlearis and soleus muscles did not differ in the experimental groups under basal conditions, however these values decreased significantly in the rats fed high-fat diet under insulin stimulation (p<0.01). Leptin treatment recovered the decreased glucose transport in epitrochlearis (p<0.05) and soleus muscles (p=0.08). Triglyceride concentrations in soleus muscles were increased significantly in the rats fed high-fat diet as compared to rats fed chow diet (p<0.01), and were decreased significantly by leptin treatment (p<0.01). The glucose transport was measured under basal conditions and after 60 microU/ml of insulin treatment with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to rats fed high-fat diet recovered impaired insulin responsiveness of skeletal muscles and muscle triglyceride concentrations. However, there was no direct stimulatory effect of leptin on insulin sensitivity of skeletal muscles in vitro. 相似文献
959.
Oh GS Pae HO Lee BS Kim BN Kim JM Kim HR Jeon SB Jeon WK Chae HJ Chung HT 《Free radical biology & medicine》2006,41(1):106-119
Hydrogen sulfide (H(2)S), a regulatory gaseous molecule that is endogenously synthesized by cystathionine gamma-lyase (CSE) and/or cystathionine beta-synthase (CBS) from L-cysteine (L-Cys) metabolism, is a putative vasodilator, and its role in nitric oxide (NO) production is unexplored. Here, we show that at noncytotoxic concentrations, H(2)S was able to inhibit NO production and inducible NO synthase (iNOS) expression via heme oxygenase (HO-1) expression in RAW264.7 macrophages stimulated with lipopolysaccharide (LPS). Both H(2)S solution prepared by bubbling pure H(2)S gas and NaSH, a H(2)S donor, dose dependently induced HO-1 expression through the activation of the extracellular signal-regulated kinase (ERK). Pretreatment with H(2)S or NaHS significantly inhibited LPS-induced iNOS expression and NO production. Moreover, NO production in LPS-stimulated macrophages that are expressing CSE mRNA was significantly reduced by the addition of L-Cys, a substrate for H(2)S, but enhanced by the selective CSE inhibitor beta-cyano-L-alanine but not by the CBS inhibitor aminooxyacetic acid. While either blockage of HO activity by the HO inhibitor, tin protoporphyrin IX, or down-regulation of HO-1 expression by HO-1 small interfering RNA (siRNA) reversed the inhibitory effects of H(2)S on iNOS expression and NO production, HO-1 overexpression produced the same inhibitory effects of H(2)S. In addition, LPS-induced nuclear factor (NF)-kappaB activation was diminished in RAW264.7 macrophages preincubated with H(2)S. Interestingly, the inhibitory effect of H(2)S on NF-kappaB activation was reversed by the transient transfection with HO-1 siRNA, but was mimicked by either HO-1 gene transfection or treatment with carbon monoxide (CO), an end product of HO-1. CO treatment also inhibited LPS-induced NO production and iNOS expression via its inactivation of NF-kappaB. Collectively, our results suggest that H(2)S can inhibit NO production and NF-kappaB activation in LPS-stimulated macrophages through a mechanism that involves the action of HO-1/CO. 相似文献
960.
Effect of heat treatment on the antioxidative and antigenotoxic activity of extracts from persimmon (Diospyros kaki L.) peel 总被引:1,自引:0,他引:1
Kim SY Jeong SM Kim SJ Jeon KI Park E Park HR Lee SC 《Bioscience, biotechnology, and biochemistry》2006,70(4):999-1002
Heat treatment of persimmon peel (PP) increased the antioxidative activity of the 70% ethanolic extract (EE) and water extract (WE) from PP. EE and WE both prevented H2O2-induced DNA damage to human peripheral lymphocytes. The antioxidative and antigenotoxic activities of the PP extracts were significantly affected by heating. 相似文献