全文获取类型
收费全文 | 636篇 |
免费 | 59篇 |
专业分类
695篇 |
出版年
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 11篇 |
2020年 | 5篇 |
2019年 | 12篇 |
2018年 | 12篇 |
2017年 | 19篇 |
2016年 | 13篇 |
2015年 | 13篇 |
2014年 | 27篇 |
2013年 | 21篇 |
2012年 | 36篇 |
2011年 | 48篇 |
2010年 | 24篇 |
2009年 | 25篇 |
2008年 | 35篇 |
2007年 | 28篇 |
2006年 | 42篇 |
2005年 | 40篇 |
2004年 | 35篇 |
2003年 | 38篇 |
2002年 | 23篇 |
2001年 | 20篇 |
2000年 | 12篇 |
1999年 | 12篇 |
1998年 | 12篇 |
1997年 | 7篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1993年 | 3篇 |
1992年 | 8篇 |
1991年 | 5篇 |
1990年 | 6篇 |
1988年 | 8篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 7篇 |
1984年 | 6篇 |
1982年 | 7篇 |
1981年 | 3篇 |
1980年 | 2篇 |
1979年 | 6篇 |
1977年 | 2篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1969年 | 3篇 |
1968年 | 3篇 |
1965年 | 3篇 |
排序方式: 共有695条查询结果,搜索用时 0 毫秒
151.
Antigenic probes locate a serum-gelsolin-interaction site on the C-terminal part of actin. 总被引:3,自引:2,他引:1 下载免费PDF全文
M Boyer J Feinberg H K Hue J P Capony Y Benyamin C Roustan 《The Biochemical journal》1987,248(2):359-364
The implication of part of the C-terminal of actin (within the 285-375 sequence) in the interaction of serum gelsolin was investigated by the use of specific antibodies. These antibodies were directed against two or three discrete epitopes, one of which was specific for skeletal-muscle actin. Some of these epitopes were found to be near the serum gelsolin-actin interface. Thus it can be assumed that part of the C-terminal of actin is exposed at the barbed end of the actin filament. The interaction between tropomyosin and actin was also studied. 相似文献
152.
Structural and functional variations in skeletal-muscle and scallop muscle actins. 总被引:1,自引:1,他引:0 下载免费PDF全文
H K Hue J P Labbé M C Harricane J C Cavadore Y Benyamin C Roustan 《The Biochemical journal》1988,256(3):853-859
Structural and functional properties in two striated-muscle actins, one from a vertebrate, the other from an invertebrate (scallop), were compared in relation to a smooth-muscle actin isoform (aortic actin). In spite of differences in the variable N-terminal region, the two striated-muscle isoactins showed, in contrast with aortic actin, a large structural homology revealed by proteinase-susceptibility and interaction with the myosin head. Thus the myosin head may bind to the two striated-muscle actins in constant parts of the 18-113 sequence. In contrast, antigenic reactivity of conformational epitopes of these actins strongly differentiated scallop actin from the two others. The behaviour of the scallop actin appears to be related to several amino acid substitutions located near or at functional domains such as monomer-monomer binding site, DNAase-I-dependent actin-actin binding site and actin-severing domain, which modified the polypeptide chain exposure. 相似文献
153.
A case of familial Leydig cell hypoplasia as a cause of male pseudohermaphroditism is described in two 46,XY female sibs. Biochemical and histologic evidence for such diagnosis is presented. 相似文献
154.
Previous studies have demonstrated that homogenates of the livers of rats contain a neutral retinyl ester hydrolase activity that requires millimolar concentrations of bile salts for maximal in vitro activity. The enzymatic properties of this neutral, bile salt-dependent retinyl ester hydrolase activity in liver homogenates are nearly identical to those observed in the present report for the in vitro hydrolysis of retinyl palmitate by purified rat pancreatic cholesteryl ester hydrolase (EC 3.1.1.13). Moreover, anti-rat pancreatic cholesteryl ester hydrolase IgG completely inhibits the bile salt-dependent retinyl ester hydrolase activity of rat liver homogenates whereas normal rabbit IgG does not. We also show that liver homogenates contain a neutral, bile salt-independent retinyl ester hydrolase activity that differs from the bile salt-dependent activity in that 1) its absolute activity does not vary markedly among individual rats, 2) it is not inhibited by antibodies to pancreatic cholesteryl ester hydrolase, and 3) it is localized in the microsomal fraction of liver homogenates. Subfractionation of microsomes demonstrates that the neutral, bile salt-independent retinyl ester hydrolase activity is associated with liver cell plasma membranes and thus may play a role in the hydrolysis of retinyl esters delivered to the liver by chylomicron remnants. 相似文献
155.
Ibrahem H.M. Ahmed Esmat F. Ali Abdelmoniem A. Gad Abdallah Bardisi Amira M. El-Tahan O.A. Abd Esadek Mohamed T. El-Saadony Ahmed S. Gendy 《Saudi Journal of Biological Sciences》2022,29(4):2291
The study aims to investigate the effect of foliar spray with three plant growth regulators (PGRs) p-Chlorophenoxyacetic acid (CPA) at 20 and 40 ppm; Gibberellic acid (GA3) at 20 and 30 ppm, 1-Naphthaleneacetic acid (NAA) at 10 and 20 ppm on the response of fruit set, yield, and fruit quality of some hot pepper cultivars (Chillina, Parbirian, Shampion, and Hyffa) grown in sandy soil under plastic tunnels as compared to the control. Spraying Chillina cultivar GA3 at 30 ppm significantly increased the number of fruits/ plant and fruit set (%), yield/plant, and total yield/fad. In addition, the contents of TSS and Vit C, furthermore, maximum capsaicin content were observed in chili fruits in both seasons. However, the interaction between Chillina cultivar and spraying with GA3 at 20 ppm ranked second in yield and quality. The interaction between Parbirian cultivars and spraying with GA3 at 20 or 30 ppm increased the number of flowers/plants in both seasons. On the other hand, the interaction between Shampion cultivar and spraying with tap water (control) gave the lowest values of the number of flowers/ plants, the number of fruits/ plant and fruit set (%), yield, and its components, and fruit quality in both seasons. 相似文献
156.
Sameh A. Gad Masaya Sugiyama Masataka Tsuge Kosho Wakae Kento Fukano Mizuki Oshima Camille Sureau Noriyuki Watanabe Takanobu Kato Asako Murayama Yingfang Li Ikuo Shoji Kunitada Shimotohno Kazuaki Chayama Masamichi Muramatsu Takaji Wakita Tomoyoshi Nozaki Hussein H. Aly 《PLoS pathogens》2022,18(3)
Intracellular transport via microtubule-based dynein and kinesin family motors plays a key role in viral reproduction and transmission. We show here that Kinesin Family Member 4 (KIF4) plays an important role in HBV/HDV infection. We intended to explore host factors impacting the HBV life cycle that can be therapeutically addressed using siRNA library transfection and HBV/NLuc (HBV/NL) reporter virus infection in HepG2-hNTCP cells. KIF4 silencing resulted in a 3-fold reduction in luciferase activity following HBV/NL infection. KIF4 knockdown suppressed both HBV and HDV infection. Transient KIF4 depletion reduced surface and raised intracellular NTCP (HBV/HDV entry receptor) levels, according to both cellular fractionation and immunofluorescence analysis (IF). Overexpression of wild-type KIF4 but not ATPase-null KIF4 mutant regained the surface localization of NTCP and significantly restored HBV permissiveness in these cells. IF revealed KIF4 and NTCP colocalization across microtubule filaments, and a co-immunoprecipitation study revealed that KIF4 interacts with NTCP. KIF4 expression is regulated by FOXM1. Interestingly, we discovered that RXR agonists (Bexarotene, and Alitretinoin) down-regulated KIF4 expression via FOXM1-mediated suppression, resulting in a substantial decrease in HBV-Pre-S1 protein attachment to HepG2-hNTCP cell surface and subsequent HBV infection in both HepG2-hNTCP and primary human hepatocyte (PXB) (Bexarotene, IC50 1.89 ± 0.98 μM) cultures. Overall, our findings show that human KIF4 is a critical regulator of NTCP surface transport and localization, which is required for NTCP to function as a receptor for HBV/HDV entry. Furthermore, small molecules that suppress or alleviate KIF4 expression would be potential antiviral candidates targeting HBV and HDV entry. 相似文献
157.
The accumulation of data on structural variation in cancer genomes provides an opportunity to better understand the mechanisms of genomic alterations and the forces of selection that act upon these alterations in cancer. Here we test evidence supporting the influence of two major forces, spatial chromosome structure and purifying (or negative) selection, on the landscape of somatic copy-number alterations (SCNAs) in cancer. Using a maximum likelihood approach, we compare SCNA maps and three-dimensional genome architecture as determined by genome-wide chromosome conformation capture (HiC) and described by the proposed fractal-globule model. This analysis suggests that the distribution of chromosomal alterations in cancer is spatially related to three-dimensional genomic architecture and that purifying selection, as well as positive selection, influences SCNAs during somatic evolution of cancer cells. 相似文献
158.
Simpson N Shaw R Crepin VF Mundy R FitzGerald AJ Cummings N Straatman-Iwanowska A Connerton I Knutton S Frankel G 《Molecular microbiology》2006,60(2):349-363
Enteropathogenic Escherichia coli (EPEC) is the single most important contributor to child diarrhoea in developing countries. Nevertheless, the mechanism responsible for EPEC diarrhoea remains elusive. Using the yeast two-hybrid system to determine the target host cell protein of the EPEC type III secretion system effector Map led to identification of ezrin/radixin/moesin (ERM)-binding phosphoprotein 50 (EBP50), also known as Na+/H+ exchanger regulatory factor 1 (NHERF1). Protein interaction is mediated by the carboxy-terminal Thr-Arg-Leu (TRL) motif of Map and the PSD-95/Disk-large/ZO-1 domain 1 (PDZ1) of EBP50/NHERF1. Although EBP50/NHERF1 is recruited to site of EPEC adhesion in a Map-independent mechanism, co-immunoprecipitation and immunostaining revealed that Map binds to, induces proteolysis of, and colocalizes with EBP50/NHERF1 during infection of cultured epithelial cells. The TRL motif of Map was involved in Map-induced filopodia formation and brush border elongation on infected HeLa and Caco-2 cells respectively. As EBP50/NHERF1 regulates ion channels in the intestine we assessed the involvement of Map in diarrhoea using the Citrobacter rodentium mouse model of EPEC. We report significantly greater diarrhoea following infections with wild-type C. rodentium compared with C. rodentiumDeltamap. These results provide new insights into the mechanisms of EPEC diarrhoea. 相似文献
159.
160.
The essential amino acid methionine is a substrate for the synthesis of S-adenosyl-methionine (SAM), that donates its methyl group to numerous methylation reactions, and from which polyamines and
ethylene are generated. To study the regulatory role of methionine synthesis in tomato fruit ripening, which requires a sharp
increase in ethylene production, we cloned a cDNA encoding cystathionine γ-synthase (CGS) from tomato and analysed its mRNA
and protein levels during tomato fruit ripening. CGS mRNA and protein levels peaked at the “turning” stage and declined as
the fruit ripened. Notably, the tomato CGS mRNA level in both leaves and fruit was negatively affected by methionine feeding,
a regulation that Arabidopsis, but not potato CGS mRNA is subject to. A positive correlation was found between elevated ethylene
production and increased CGS mRNA levels during the ethylene burst of the climacteric ripening of tomato fruit. In addition,
wounding of pericarp from tomato fruit at the mature green stage stimulated both ethylene production and CGS mRNA level. Application
of exogenous methionine to pericarp of mature green fruit increased ethylene evolution, suggesting that soluble methionine
may be a rate limiting metabolite for ethylene synthesis. Moreover, treatment of mature green tomato fruit with the ethylene-releasing
reagent Ethephon caused an induction of CGS mRNA level, indicating that CGS gene expression is regulated by ethylene. Taken
together, these results imply that in addition to recycling of the methionine moieties via the Yang pathway, operating during
synthesis of ethylene, de novo synthesis of methionine may be required when high rates of ethylene production are induced. 相似文献