全文获取类型
收费全文 | 322篇 |
免费 | 29篇 |
国内免费 | 1篇 |
专业分类
352篇 |
出版年
2023年 | 8篇 |
2022年 | 6篇 |
2021年 | 14篇 |
2020年 | 11篇 |
2019年 | 17篇 |
2018年 | 18篇 |
2017年 | 20篇 |
2016年 | 22篇 |
2015年 | 18篇 |
2014年 | 15篇 |
2013年 | 28篇 |
2012年 | 31篇 |
2011年 | 25篇 |
2010年 | 16篇 |
2009年 | 12篇 |
2008年 | 14篇 |
2007年 | 11篇 |
2006年 | 16篇 |
2005年 | 15篇 |
2004年 | 15篇 |
2003年 | 9篇 |
2002年 | 4篇 |
2001年 | 2篇 |
2000年 | 1篇 |
1998年 | 2篇 |
1997年 | 1篇 |
1995年 | 1篇 |
排序方式: 共有352条查询结果,搜索用时 0 毫秒
31.
Franziska Todt Zeynep Cakir Frank Reichenbach Frederic Emschermann Joachim Lauterwasser Andrea Kaiser Gabriel Ichim Stephen WG Tait Stephan Frank Harald F Langer Frank Edlich 《The EMBO journal》2015,34(1):67-80
The Bcl-2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane and commit cells to apoptosis. Pro-survival Bcl-2 proteins control Bax by constant retrotranslocation into the cytosol of healthy cells. The stabilization of cytosolic Bax raises the question whether the functionally redundant but largely mitochondrial Bak shares this level of regulation. Here we report that Bak is retrotranslocated from the mitochondria by pro-survival Bcl-2 proteins. Bak is present in the cytosol of human cells and tissues, but low shuttling rates cause predominant mitochondrial Bak localization. Interchanging the membrane anchors of Bax and Bak reverses their subcellular localization compared to the wild-type proteins. Strikingly, the reduction of Bax shuttling to the level of Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis induction. Thus, fast Bax retrotranslocation is required to protect cells from commitment to programmed death. 相似文献
32.
Ines Pires da Silva Isabella C. Glitza Lauren E. Haydu Romany Johnpulle Patricia D. Banks George D. Grass Simone M. A. Goldinger Jessica L. Smith Ashlyn S. Everett Peter Koelblinger Rachel Roberts‐Thomson Michael Millward Victoria G. Atkinson Alexander Guminski Rony Kapoor Robert M. Conry Matteo S. Carlino Wei Wang Mark J. Shackleton Zeynep Eroglu Serigne Lo Angela M. Hong Georgina V. Long Douglas B. Johnson Alexander M. Menzies 《Pigment cell & melanoma research》2019,32(4):553-563
33.
Myosin VI is a molecular motor that can walk processively on actin filaments with a 36-nm step size. The walking mechanism of myosin VI is controversial because it takes very large steps without an apparent lever arm of required length. Therefore, myosin VI is argued to be the first exception to the widely established lever arm theory. It is therefore critical to directly demonstrate whether this motor walks hand-over-hand along actin despite its short lever arm. Here, we follow the displacement of a single myosin VI head during the stepping process. A single head is displaced 72 nm during stepping, whereas the center of mass previously has been shown to move 36 nm. The most likely explanation for this result is a hand-over-hand walking mechanism. We hypothesize the existence of a flexible element that would allow the motor to bridge the observed 72-nm distance. 相似文献
34.
DNA damage and antioxidant defense in peripheral leukocytes of patients with Type I diabetes mellitus 总被引:3,自引:0,他引:3
We determined relationship among DNA damage, nitric oxide (NO) and antioxidant defense in leukocytes of patients with Type 1 DM. DNA damage was evaluated as strand breakage and formamidopyrimidine DNA glycosylase (Fpg)-sensitive sites by the comet assay in DNA from leukocytes of the subjects. Nitrite level, as a product of NO, superoxide dismutase (SOD) activity and glutathione peroxidase (G-Px) activity of the leukocytes were measured by spectrophotometric kits. Serum glucose level and glycosylated haemoglobin (HbA(1c)) were higher in the patients, as expected. Differences in measured parameters between controls and patients were assessed in men and women separately. There was no significant difference between patient and control groups in neither men nor women for nitrite level. Strand breakage and Fpg-sensitive sites were found to be increased, SOD and G-Px activities of the leukocytes were found to be decreased in both men and women of patient group as compared to their respective controls. Significant correlations were determined between strand breakage and HbA(1c) (r = 0.37, P<0.05); Fpg-sensitive sites and HbA(1c) (r = 0.59, P<0.01); Fpg-sensitive sites and glucose (r = 0.45, P<0.02); Fpg-sensitive sites and SOD (r = -0.48, P<0.02); HbA(1c) and SOD (r = -0.50, P<0.02). In conclusion, impaired antioxidant defense in leukocytes of patients with Type 1 DM may be one of the responsible mechanisms for increased DNA damage in those patients. 相似文献
35.
Equils O Madak Z Liu C Michelsen KS Bulut Y Lu D 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(12):7642-7646
Opportunistic infections, common in HIV-1-infected patients, increase HIV replication; however, the intracellular signaling mechanisms involved are not clearly known. We have shown that Toll-like receptor 2 (TLR2), TLR4, and TLR9 mediate microbial Ag-induced HIV-long terminal repeat (HIV-LTR) trans-activation and HIV-1 replication, and that LPS-induced HIV-LTR trans-activation is mediated through myeloid differentiation adapter protein. Recently, Toll-IL-1R domain-containing adapter protein (TIRAP) has been identified as an adapter molecule that mediates responses to TLR2 and TLR4 ligands, and TIRAP was suggested to provide signaling specificity for different TLRs. Rac1, a small GTP-binding protein that is activated upon LPS stimulation of macrophages, activates phosphatidylinositol 3-kinase and Akt and leads to NF-kappaB activation. The roles of Rac1 and TIRAP in LPS activation of HIV replication is not known. In the present study we show that LPS stimulation of human microvessel endothelial cells leads to Rac1 activation. Constitutively active Rac1 (Rac1V12) simulated the effect of LPS to activate HIV-LTR, whereas the expression of dominant negative Rac1 (Rac1N17) partially blocked LPS-induced HIV-LTR trans-activation. Rac1V12-induced HIV-LTR activation was independent of myeloid differentiation adapter protein, and dominant negative TIRAP blocked Rac1V12-induced HIV-LTR trans-activation. In this study we show for the first time that activation of Rac1 leads to HIV-LTR trans-activation, and this is mediated through TIRAP. Together these results underscore the importance of Rac1 and TIRAP in TLR4 activation of HIV replication and help delineate the signaling pathways induced by TLRs to mediate microbial Ag-induced HIV replication and HIV pathogenesis. 相似文献
36.
Size‐based interactions and trophic transfer efficiency are modified by fish predation and cyanobacteria blooms in Lake Mývatn,Iceland 下载免费PDF全文
Zeynep Ersoy Erik Jeppesen Serena Sgarzi Ignasi Arranz Miguel Cañedo‐Argüelles Xavier D. Quintana Frank Landkildehus Torben L. Lauridsen Mireia Bartrons Sandra Brucet 《Freshwater Biology》2017,62(11):1942-1952
37.
38.
Soner Kılıcaslan Mustafa Arslan Zeynep Ruya Çigdem Bilen Adem Ergün 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):1300-1305
Sulfonamide-bearing thiazole compounds were synthesized and their inhibitory effects on the activity of purified human carbonic anhydrase I and II were evaluated. Human carbonic anhydrase isoenzymes (hCA-I and hCA-II) were purified from erythrocyte cells by affinity chromatography. The inhibitory effects of the 12 synthesized sulfonamide (5a–l) on the hydratase and esterase activities of these isoenzymes (hCA-I and hCA-II) were studied in vitro. In relation to these activities, the inhibition equilibrium constants (Ki) were determined. The results showed that all the synthesized compounds inhibited the CA isoenzyme activity. Among them 5b was found to be the most active (IC50?=?0.35?μM; Ki: 0.33?μM) for hCA I and hCA II. 相似文献
39.
The functional response of a predator describes the rate at which it kills its prey at different prey densities and is, therefore, an important tool to determine the efficiency of a predator in regulating the population dynamics of a prey. We investigated the functional response of Coccinella septempunctata L. (Coleoptera: Coccinellidae) to varying densities of Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). The results revealed that the linear coefficient, P1 in the reduced logistic model was found significantly negative for the 4th instar larvae and adult male and female of C. septempunctata (?0.002, ?0.004 and???0.002, respectively) indicating a type II functional response. The parameter estimates of adult male, female and 4thinstar larvae of C. septempunctata calculated through Holling's disc model revealed that the highest attack rate (a) (1.047?±?0.014), shortest handling time (Th) (0.0984?±?0.024?h) and largest maximum capture rate (T/Th) (243.902) was exhibited by female. Parameter estimates calculated through Rogers’s equation also showed the same sequence where maximum attack rate (a) of 0.00256?±?0.0003 was exhibited by female followed by 4th instar larvae (0.00251?±?0.0005). The shortest handling time (Th) (0.210?±?0.003?h) and highest maximum capture rate (T/Th) (114.17) was also exhibited by female. Comparison of functional response curves of adult male, female and 4th instar larvae revealed that maximum consumption of prey at all the densities offered was shown by female followed by 4thinstar larvae. The study manifested that C. septempunctata could be an efficient biocontrol agent of pea aphid, A. pisum. 相似文献
40.
Zeynep Ermis Karaali Seyma Sozen Melis Yurdum Canan Cacina Bahar Toptas Ozlem Gok Bedia Agachan 《Molecular biology reports》2010,37(7):3615-3619
Inflammation is a crucial component of coronary atherosclerosis and myocardial infarction (MI). Chemokine receptors are important
modulators of inflammation. Polymorphisms in genes coding for chemokine receptors, CCR2 and CCR5, have been studied as genetic markers of coronary artery
disease. In the present study, we investigated whether genetic variants of CCR2-V64I and CCR5-delta32 chemokine receptors
have any effect on the development of myocardial infarction. A total of 146 MI patients and 202 control subjects were genotyped
for CCR2 and CCR5. CCR2-V64I genotypes were not significantly different between patients with MI and controls (P > 0.05). CCR5-delta32 genotype distribution in cases was significantly different from that of controls (P = 0.042). The CCR5-delta32 wt/deletion genotype frequencies for controls and cases were 0.10 and 0.19, respectively and individuals
with CCR5-delta32 wt/deletion genotype had a 2.13-fold increased risk of myocardial infarction (P = 0.0013). Individuals carrying the CCR5-delta32 heterozygote or homozygous variant genotype (deletion/deletion + wt/deletion)
had a 1.96-fold increased risk of myocardial infarction compared with the wild-type genotype (wt/wt) (p: 0.016). In conclusion,
our data have suggested that genetic variant of CCR5 might be associated with the development of MI. Further larger sample
size studies are required to confirm our findings. 相似文献