全文获取类型
收费全文 | 530篇 |
免费 | 42篇 |
国内免费 | 1篇 |
出版年
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 4篇 |
2019年 | 6篇 |
2018年 | 9篇 |
2017年 | 11篇 |
2016年 | 9篇 |
2015年 | 28篇 |
2014年 | 17篇 |
2013年 | 28篇 |
2012年 | 37篇 |
2011年 | 43篇 |
2010年 | 15篇 |
2009年 | 28篇 |
2008年 | 13篇 |
2007年 | 27篇 |
2006年 | 33篇 |
2005年 | 29篇 |
2004年 | 26篇 |
2003年 | 24篇 |
2002年 | 18篇 |
2001年 | 12篇 |
2000年 | 16篇 |
1999年 | 12篇 |
1998年 | 21篇 |
1997年 | 5篇 |
1996年 | 6篇 |
1995年 | 2篇 |
1994年 | 10篇 |
1992年 | 6篇 |
1991年 | 5篇 |
1990年 | 3篇 |
1989年 | 5篇 |
1988年 | 3篇 |
1987年 | 3篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 2篇 |
1982年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 5篇 |
1976年 | 2篇 |
1973年 | 1篇 |
1972年 | 5篇 |
1971年 | 2篇 |
排序方式: 共有573条查询结果,搜索用时 15 毫秒
91.
Chien-Chang Chiu Jin-Chuan Sheu Chien-Hung Chen Cha-Ze Lee Ling-Ling Chiou Shiu-Huey Chou Guan-Tarn Huang Hsuan-Shu Lee 《Histochemistry and cell biology》2009,132(5):479-489
Liver progenitors, so-called oval cells, proliferate remarkably from periportal areas after severe liver injury when hepatocyte
regeneration is compromised. These cells invade far into the liver parenchyma. Molecular mechanisms underlying these behaviors
of oval cells remain poorly understood. In this study, we treated rats with 2-acetylaminofluorene/carbon tetrachloride to
induce hepatic oval cells. By expression microarray analysis, we investigated global gene expression profiles in liver tissue,
with an emphasis on adhesion molecules, extracellular matrix proteins, matrix metalloproteinases (MMPs), growth factors/cytokines,
and receptors that might contribute to the distinct behaviors of oval cells. Genes upregulated at least twofold were selected.
We then performed immunostaining to verify the microarray results and identified expression of MMP-7 and CD44 in oval cells.
Staining of cytokeratin (CK)-19, an oval-cell marker, was similar between oval cells located next to periportal areas and
those located far within the parenchyma. In contrast, CD44 staining was more intense in the parenchyma than in periportal
areas, suggesting a role of CD44 in oval-cell invasion. Moreover, newly differentiated CK-19+ hepatocytes within foci did not show CD44 staining, suggesting that CD44 is related to the undifferentiated oval-cell phenotype.
We then investigated oval-cell reactivity in CD44-deficient mice fed an oval cell-inducing diet of 3,5-diethoxycarbonyl-1,4-dihydrocollidine.
Results showed significantly reduced oval-cell reactivity in CD44-deficient mice. Thus, oval cells express MMP-7 and CD44,
and CD44 appears to play critical roles in the proliferation, invasion, and differentiation of hepatic oval cells in rodents. 相似文献
92.
93.
94.
Serum Level of Trefoil Factor 2 can Predict the Extent of Gastric Spasmolytic Polypeptide‐Expressing Metaplasia in the H. pylori‐Infected Gastric Cancer Relatives 下载免费PDF全文
95.
A high-performance liquid chromatography (HPLC)-based fluorometric method for measuring serine hydroxymethyltransferase (SHMT) activity toward formation of serine and (6S)-H4PteGlun has been developed. In this method, serine formed by SHMT activity is reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) to form the fluorescent adduct NBD–serine. The fluorescent assay components are then separated by reversed-phase chromatography, and NBD–serine is quantified by comparison with standards. This method was used to determine the Km and kcat values for 5,10-CH2–H4PteGlu5 of an SHMT from Arabidopsis thaliana. These data represent the first determination of kinetic parameters for (6S)-5,10-CH2–H4PteGlu5 for an SHMT from any organism. 相似文献
96.
97.
Yang FL Yang YL Liao PC Chou JC Tsai KC Yang AS Sheu F Lin TL Hsieh PF Wang JT Hua KF Wu SH 《The Journal of biological chemistry》2011,286(24):21041-21051
The active components of a primary pyrogenic liver abscess (PLA) Klebsiella pneumoniae in stimulating cytokine expression in macrophages are still unclear. The capsular polysaccharide (CPS) of PLA K. pneumoniae is important in determining clinical manifestations, and we have shown that it consists of repeating units of the trisaccharide (→3)-β-D-Glc-(1→4)-[2,3-(S)-pyruvate]-β-D-GlcA-(1→4)-α-L-Fuc-(1→) and has the unusual feature of extensive pyruvation of glucuronic acid and acetylation of C(2)-OH or C(3)-OH of fucose. We demonstrated that PLA K. pneumoniae CPS induces secretion of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) by macrophages through Toll-like receptor 4 (TLR4) and that this effect was lost when pyruvation and O-acetylation were chemically destroyed. Furthermore, expression of TNF-α and IL-6 in PLA K. pneumoniae CPS-stimulated macrophages was shown to be regulated by the TLR4/ROS/PKC-δ/NF-κB, TLR4/PI3-kinase/AKT/NF-κB, and TLR4/MAPK signaling pathways. 相似文献
98.
Lin MH Yang YL Chen YP Hua KF Lu CP Sheu F Lin GH Tsay SS Liang SM Wu SH 《The Journal of biological chemistry》2011,286(20):17736-17745
Bacterial polysaccharides are known to induce the immune response in macrophages. Here we isolated a novel extracellular polysaccharide from the biofilm of Thermus aquaticus YT-1 and evaluated its structure and immunomodulatory effects. The size of this polysaccharide, TA-1, was deduced by size-exclusion chromatography as 500 kDa. GC-MS, high performance anion-exchange chromatography with pulsed amperometric detection, electrospray ionization-MS/MS, and NMR revealed the novel structure of TA-1. The polysaccharide is composed of tetrasaccharide-repeating units of galactofuranose, galactopyranose, and N-acetylgalactosamine (1:1:2) and lacked acidic sugars. TA-1 stimulated macrophage cells to produce the cytokines TNF-α and IL-6. Screening of Toll-like receptors and antibody-blocking experiments indicated that the natural receptor of TA-1 in its immunoactivity is TLR2. Recognition of TA-1 by TLR2 was confirmed by TA-1 induction of IL-6 production in peritoneal macrophages from wild-type mice but not from TLR2(-/-) mice. TA-1, as a TLR2 agonist, could possibly be used as an adjuvant and could enhance cytokine release, which increases the immune response. Furthermore, TA-1 induced cytokine release is dependent on MyD88/TIRAP. 相似文献
99.
Ryu SY Beutner G Kinnally KW Dirksen RT Sheu SS 《The Journal of biological chemistry》2011,286(24):21324-21329
Heart mitochondria utilize multiple Ca(2+) transport mechanisms. Among them, the mitochondrial ryanodine receptor provides a fast Ca(2+) uptake pathway across the inner membrane to control "excitation and metabolism coupling." In the present study, we identified a novel ryanodine-sensitive channel in the native inner membrane of heart mitochondria and characterized its pharmacological and biophysical properties by directly patch clamping mitoplasts. Four distinct channel conductances of ~100, ~225, ~700, and ~1,000 picosiemens (pS) in symmetrical 150 mm CsCl were observed. The 225 pS cation-selective channel exhibited multiple subconductance states and was blocked by high concentrations of ryanodine and ruthenium red, known inhibitors of ryanodine receptors. Ryanodine exhibited a concentration-dependent modulation of this channel, with low concentrations stabilizing a subconductance state and high concentrations abolishing activity. The 100, 700, and 1,000 pS conductances exhibited different channel characteristics and were not inhibited by ryanodine. Taken together, these findings identified a novel 225 pS channel as the native mitochondrial ryanodine receptor channel activity in heart mitoplasts with biophysical and pharmacological properties that distinguish it from previously identified mitochondrial ion channels. 相似文献
100.
Electrochemical (EC) sensing approaches have exploited the use of carbon nanotubes (CNTs) as electrode materials owing to their unique structures and properties to provide strong electrocatalytic activity with minimal surface fouling. Nanofabrication and device integration technologies have emerged along with significant advances in the synthesis, purification, conjugation and biofunctionalization of CNTs. Such combined efforts have contributed towards the rapid development of CNT-based sensors for a plethora of important analytes with improved detection sensitivity and selectivity. The use of CNTs opens an opportunity for the direct electron transfer between the enzyme and the active electrode area. Of particular interest are also excellent electrocatalytic activities of CNTs on the redox reaction of hydrogen peroxide and nicotinamide adenine dinucleotide, two major by-products of enzymatic reactions. This excellent electrocatalysis holds a promising future for the simple design and implementation of on-site biosensors for oxidases and dehydrogenases with enhanced selectivity. To date, the use of an anti-interference layer or an artificial electron mediator is critically needed to circumvent unwanted endogenous electroactive species. Such interfering species are effectively suppressed by using CNT based electrodes since the oxidation of NADH, thiols, hydrogen peroxide, etc. by CNTs can be performed at low potentials. Nevertheless, the major future challenges for the development of CNT-EC sensors include miniaturization, optimization and simplification of the procedure for fabricating CNT based electrodes with minimal non-specific binding, high sensitivity and rapid response followed by their extensive validation using “real world” samples. A high resistance to electrode fouling and selectivity are the two key pending issues for the application of CNT-based biosensors in clinical chemistry, food quality and control, waste water treatment and bioprocessing. 相似文献