全文获取类型
收费全文 | 689篇 |
免费 | 49篇 |
出版年
2022年 | 4篇 |
2021年 | 10篇 |
2020年 | 8篇 |
2019年 | 4篇 |
2018年 | 14篇 |
2017年 | 6篇 |
2016年 | 13篇 |
2015年 | 25篇 |
2014年 | 38篇 |
2013年 | 49篇 |
2012年 | 59篇 |
2011年 | 43篇 |
2010年 | 36篇 |
2009年 | 31篇 |
2008年 | 36篇 |
2007年 | 36篇 |
2006年 | 36篇 |
2005年 | 22篇 |
2004年 | 19篇 |
2003年 | 12篇 |
2002年 | 27篇 |
2001年 | 15篇 |
2000年 | 17篇 |
1999年 | 13篇 |
1998年 | 9篇 |
1997年 | 11篇 |
1996年 | 11篇 |
1995年 | 7篇 |
1994年 | 6篇 |
1993年 | 7篇 |
1992年 | 22篇 |
1991年 | 13篇 |
1990年 | 9篇 |
1989年 | 14篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 4篇 |
1985年 | 8篇 |
1984年 | 3篇 |
1981年 | 1篇 |
1980年 | 1篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 3篇 |
1974年 | 2篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1969年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有738条查询结果,搜索用时 633 毫秒
101.
Chromosomal Location Plays a Role in Regulation of Aflatoxin Gene Expression in Aspergillus parasiticus 总被引:1,自引:0,他引:1
下载免费PDF全文
![点击此处可从《Applied microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Ching-Hsun Chiou Michael Miller David L. Wilson Frances Trail John E. Linz 《Applied microbiology》2002,68(1):306-315
The nor-1 gene in the filamentous fungus Aspergillus parasiticus encodes a ketoreductase involved in aflatoxin biosynthesis. To study environmental influences on nor-1 expression, we generated plasmid pAPGUSNNB containing a nor-1 promoter-β-glucuronidase (GUS) (encoded by uidA) reporter fusion with niaD (encodes nitrate reductase) as a selectable marker. niaD transformants of A. parasiticus strain NR-1 (niaD) carried pAPGUSNNB integrated predominantly at the nor-1 or niaD locus. Expression of the native nor-1 and nor-1::GUS reporter was compared in transformants grown under aflatoxin-inducing conditions by Northern and Western analyses and by qualitative and quantitative GUS activity assays. The timing and level of nor-1 promoter function with pAPGUSNNB integrated at nor-1 was similar to that observed for the native nor-1 gene. In contrast, nor-1 promoter activity in pAPGUSNNB and a second nor-1::GUS reporter construct, pBNG3.0, was not detectable when integration occurred at niaD. Because niaD-dependent regulation could account for the absence of expression at niaD, a third chromosomal location was analyzed using pAPGUSNP, which contained nor-1::GUS plus pyrG (encodes OMP decarboxylase) as a selectable marker. GUS expression was detectable only when pAPGUSNP integrated at nor-1 and was not detectable at pyrG, even under growth conditions that required pyrG expression. nor-1::GUS is regulated similarly to the native nor-1 gene when it is integrated at its homologous site within the aflatoxin gene cluster but is not expressed at native nor-1 levels at two locations outside of the aflatoxin gene cluster. We conclude that the GUS reporter system can be used effectively to measure nor-1 promoter activity and that nor-1 is subject to position-dependent regulation in the A. parasiticus chromosome. 相似文献
102.
Leu-enkephalin is one of the important peptides which could become useful drugs in the clinics because of its analgesic action and its availability in mass quantity through biotechnology production. It is found in this study that enkephalin can be effectively absorbed systemically through eyes without using a surfactant as absorption enhancer. Enkephalin at 0.125% (31.25 micrograms/25 microliter) reached a plateau of blood concentration at 11.5 ng/ml in 3-4 hrs and stayed high for 8-9 hrs. In contrast, the blood concentration of enkephalin declined rapidly after i.v. administration with a T1/2 of less than 30 min and reached the lowest point at 22 ng/ml in 5 hrs. With higher concentrations at 1% (.25 mg/25 microliter) and 5% (1.25 mg/25 microliter) similar absorption kinetics was observed except that they reached higher plateau of blood concentration at 72 ng/ml and 233 ng/ml, respectively. 相似文献
103.
K.-H. Hsu P. Brandt-Rauf T.-M. Lin H.-Y. Chiou C.-H. Tseng C.-J. Chen 《Biomarkers》2013,18(6):538-546
AbstractEpidemiological studies have demonstrated an association between long-term exposure to inorganic arsenic and the related adverse effects such as cancers, skin lesions, and vascular diseases. Although several hypotheses have been proposed for the mechanism of arsenic-induced pathogenesis, it remains imperfectly understood. Recent studies have suggested that alterations in growth signal transduction pathways, particularly involving transforming growth factor-alpha (TGF-alpha), may be important. Immunoassays were used to determine the plasma levels of TGF-alpha and epidermal growth factor receptor (EGFR), which is the receptor for TGF-alpha, in residents of an arseniasis area of Taiwan in relation to their estimated cumulative arsenic exposure from drinking water. No relationship between arsenic exposure and EGFR was found. However, among the high cumulative exposure group (>6 ppm-years), levels of plasma TGF-alpha (25.5±38.2 pg ml?1) and the proportion of individuals with TGF-alpha over-expression (29.4%) were significantly higher (p<0.05) than normal, healthy unexposed controls (8.1±5.6 pg ml?1, 8.6%, respectively). There was a significant linear trend between cumulative arsenic exposure and the prevalence of plasma TGF-alpha over-expression after adjusting for age and sex (p=0.019). The results suggest that plasma TGF-alpha expression may be a useful biomarker when detecting adverse effects on arsenic exposed population. 相似文献
104.
S H Chiou 《International journal of peptide and protein research》1987,30(1):108-116
Lens crystallins were isolated from the homogenate of frog (Rana catesbeiana) eye lenses by gel permeation chromatography and characterized by gel electrophoresis, amino acid analysis and circular dichroism. Four well-defined fractions corresponding to alpha/beta-, beta-, frog 39.5 kDa and gamma-crystallins comprising the relative weight percentages in the total soluble cytoplasmic proteins of 18%, 15%, 14% and 48% respectively were obtained. The native molecular masses for each purified fraction were determined to be 432, 207, 40 and 23 kDa, respectively. The polypeptide compositions as determined by SDS-gel electrophoresis revealed the typical subunit structures of mammalian crystallins with the exception of 39.5 kDa monomeric crystallin, which has not been shown in other classes of vertebrate lenses. The spectra of circular dichroism indicate a predominant beta-sheet structure in all four fractions, which also bears a resemblance to the secondary structure of mammalian crystallins. Comparison of the amino acid compositions of frog crystallins with those of mammalian and fish crystallins suggests that gamma-crystallin from the frog is more closely related to that of porcine than fish crystallins, and the frog 39.5 kDa, frog beta- and lamprey 48 kDa crystallins are probably mutually interrelated. 相似文献
105.
106.
S H Chiou P Azari M E Himmel P G Squire 《International journal of peptide and protein research》1979,13(4):409-417
The soluble proteins from bovine lens homogenate were separated on Sepharose CL-6B (2 X 200 cm) in 0.05 M tris-NaHSO3 pH 8.2 buffer containing 20 mM EDTA. Five sharp and defined fractions (HM alpha, alpha, beta H, beta L, gamma) were obtained. Each crystallin fraction was further purified by rechromatography on the same column. Each protein fraction was pure as judged by ultracentrifugation and SDS-gel electrophoresis. The molecular weights of the five fractions were 3.04 x 10(6), 5.83 x 10(5), 1.58 x 10(5) , 4.59 x 10(4), 2.14 x 10(4) as determined from sedimentation coefficient and intrinsic viscosity data by Scheraga-Mandelkern equation, which was in close agreement with that obtained by gel filtration. The polypeptide composition of crystallins as determined by SDS-gel electrophoresis revealed one band for high molecular weight alpha (HM alpha) and alpha, three for beta H, two for beta L and one for gamma. The gross CD patterns of crystallins were about the same in the peptide region (200 nm similar to or approximately 250 nm) with a minimum centered at about 217 nm, indicative of a beta-sheet structure in all crystallins. The [theta] values at 217 nm ranged from --1700 to --3700 degrees cm2 per decimole. The CD spectra of these crystallins in the aromatic region (250 nm similar to or approximately 300 nm) were different, reflecting the different contributions of aromatic amino acids to the tertiary structure of crystallins. 相似文献
107.
108.
109.
Caveolin‐1 down‐regulation is required for Wnt5a‐Frizzled 2 signalling in Ha‐RasV12‐induced cell transformation
下载免费PDF全文
![点击此处可从《Journal of cellular and molecular medicine》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hsiu‐Kuan Lin Hsi‐Hui Lin Yu‐Wei Chiou Ching‐Lung Wu Wen‐Tai Chiu Ming‐Jer Tang 《Journal of cellular and molecular medicine》2018,22(5):2631-2643
Caveolin‐1 (Cav1) is down‐regulated during MK4 (MDCK cells harbouring inducible Ha‐RasV12 gene) transformation by Ha‐RasV12. Cav1 overexpression abrogates the Ha‐RasV12‐driven transformation of MK4 cells; however, the targeted down‐regulation of Cav1 is not sufficient to mimic this transformation. Cav1‐silenced cells, including MK4/shCav1 cells and MDCK/shCav1 cells, showed an increased cell area and discontinuous junction‐related proteins staining. Cellular and mechanical transformations were completed when MDCK/shCav1 cells were treated with medium conditioned by MK4 cells treated with IPTG (MK4+I‐CM) but not with medium conditioned by MK4 cells. Nanoparticle tracking analysis showed that Ha‐RasV12‐inducing MK4 cells increased exosome‐like microvesicles release compared with their normal counterparts. The cellular and mechanical transformation activities of MK4+I‐CM were abolished after heat treatment and exosome depletion and were copied by exosomes derived from MK4+I‐CM (MK4+I‐EXs). Wnt5a, a downstream product of Ha‐RasV12, was markedly secreted by MK4+I‐CM and MK4+I‐EXs. Suppression of Wnt5a expression and secretion using the porcupine inhibitor C59 or Wnt5a siRNA inhibited the Ha‐RasV12‐ and MK4+I‐CM‐induced transformation of MK4 cells and MDCK/shCav1 cells, respectively. Cav1 down‐regulation, either by Ha‐RasV12 or targeted shRNA, increased frizzled‐2 (Fzd2) protein levels without affecting its mRNA levels, suggesting a novel role of Cav1 in negatively regulating Fzd2 expression. Additionally, silencing Cav1 facilitated the internalization of MK4+I‐EXs in MDCK cells. These data suggest that Cav1‐dependent repression of Fzd2 and exosome uptake is potentially relevant to its antitransformation activity, which hinders the activation of Ha‐RasV12‐Wnt5a‐Stat3 pathway. Altogether, these results suggest that both decreasing Cav1 and increasing exosomal Wnt5a must be implemented during Ha‐RasV12‐driven cell transformation. 相似文献
110.