全文获取类型
收费全文 | 663篇 |
免费 | 54篇 |
国内免费 | 1篇 |
出版年
2022年 | 7篇 |
2021年 | 14篇 |
2020年 | 3篇 |
2019年 | 4篇 |
2018年 | 13篇 |
2017年 | 13篇 |
2016年 | 7篇 |
2015年 | 23篇 |
2014年 | 24篇 |
2013年 | 33篇 |
2012年 | 31篇 |
2011年 | 39篇 |
2010年 | 26篇 |
2009年 | 32篇 |
2008年 | 31篇 |
2007年 | 42篇 |
2006年 | 35篇 |
2005年 | 28篇 |
2004年 | 21篇 |
2003年 | 29篇 |
2002年 | 24篇 |
2001年 | 11篇 |
2000年 | 12篇 |
1999年 | 11篇 |
1998年 | 16篇 |
1997年 | 8篇 |
1996年 | 8篇 |
1995年 | 10篇 |
1994年 | 11篇 |
1993年 | 9篇 |
1992年 | 8篇 |
1990年 | 7篇 |
1989年 | 9篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 7篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1977年 | 9篇 |
1975年 | 3篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1923年 | 3篇 |
1899年 | 3篇 |
排序方式: 共有718条查询结果,搜索用时 854 毫秒
61.
BiP and calreticulin form an abundant complex that is independent of endoplasmic reticulum stress 总被引:5,自引:1,他引:4
下载免费PDF全文
![点击此处可从《The Plant cell》网站下载免费的PDF全文](/ch/ext_images/free.gif)
BiP is found in association with calreticulin, both in the presence and absence of endoplasmic reticulum stress. Although the BiP-calreticulin complex can be disrupted by ATP, several properties suggest that the calreticulin associated with BiP is neither unfolded nor partially or improperly folded. (1) The complex is stable in vivo and does not dissociate during 8 hr of chase. (2) When present in the complex, calreticulin masks epitopes at the C terminus of BiP that are not masked when BiP is bound to an assembly-defective protein. And (3) overproduction of calreticulin does not lead to the recruitment of more BiP into complexes with calreticulin. The BiP-calreticulin complex can be disrupted by low pH but not by divalent cation chelators. When the endoplasmic reticulum retention signal of BiP is removed, complex formation with calreticulin still occurs, and this explains the poor secretion of the truncated molecule. Gel filtration experiments showed that BiP and calreticulin are present in distinct high molecular weight complexes in which both molecules interact with each other. The possible functions of this complex are discussed. 相似文献
62.
Laura J. Mares Alvaro Garcia Helge H. Rasmussen Flemming Cornelius Yasser A. Mahmmoud Joshua R. Berlin Bogdan Lev Toby W. Allen Ronald J. Clarke 《Biophysical journal》2014
The charge-transporting activity of the Na+,K+-ATPase depends on its surrounding electric field. To isolate which steps of the enzyme’s reaction cycle involve charge movement, we have investigated the response of the voltage-sensitive fluorescent probe RH421 to interaction of the protein with BTEA (benzyltriethylammonium), which binds from the extracellular medium to the Na+,K+-ATPase’s transport sites in competition with Na+ and K+, but is not occluded within the protein. We find that only the occludable ions Na+, K+, Rb+, and Cs+ cause a drop in RH421 fluorescence. We conclude that RH421 detects intramembrane electric field strength changes arising from charge transport associated with conformational changes occluding the transported ions within the protein, not the electric fields of the bound ions themselves. This appears at first to conflict with electrophysiological studies suggesting extracellular Na+ or K+ binding in a high field access channel is a major electrogenic reaction of the Na+,K+-ATPase. All results can be explained consistently if ion occlusion involves local deformations in the lipid membrane surrounding the protein occurring simultaneously with conformational changes necessary for ion occlusion. The most likely origin of the RH421 fluorescence response is a change in membrane dipole potential caused by membrane deformation. 相似文献
63.
Magnus Kjaergaard Ann‒Beth Nørholm Ruth Hendus‒Altenburger Stine F. Pedersen Flemming M. Poulsen Birthe B. Kragelund 《Protein science : a publication of the Protein Society》2010,19(8):1555-1564
Structural characterization of intrinsically disordered proteins (IDPs) is mandatory for deciphering their potential unique physical and biological properties. A large number of circular dichroism (CD) studies have demonstrated that a structural change takes place in IDPs with increasing temperature, which most likely reflects formation of transient α-helices or loss of polyproline II (PPII) content. Using three IDPs, ACTR, NHE1, and Spd1, we show that the temperature-induced structural change is common among IDPs and is accompanied by a contraction of the conformational ensemble. This phenomenon was explored at residue resolution by multidimensional NMR spectroscopy. Intrinsic chemical shift referencing allowed us to identify regions of transiently formed helices and their temperature-dependent changes in helicity. All helical regions were found to lose rather than gain helical structures with increasing temperature, and accordingly these were not responsible for the change in the CD spectra. In contrast, the nonhelical regions exhibited a general temperature-dependent structural change that was independent of long-range interactions. The temperature-dependent CD spectroscopic signature of IDPs that has been amply documented can be rationalized to represent redistribution of the statistical coil involving a general loss of PPII conformations. 相似文献
64.
Mette Kristensen Francesco Savorani Gitte Ravn-Haren Morten Poulsen Jaroslaw Markowski Flemming H. Larsen Lars O. Dragsted Søren B. Engelsen 《Metabolomics : Official journal of the Metabolomic Society》2010,6(1):129-136
Risk of cardiovascular disease is related to cholesterol distribution in different lipoprotein fractions. Lipoproteins in
rodent model studies can only reliably be measured by time- and plasma-consuming fractionation. An alternative method to measure
cholesterol distribution in the lipoprotein fractions in rat plasma is presented in this paper. Plasma from two rat studies
(n = 68) was used in determining the lipoprotein profile by an established ultracentrifugation method and proton nuclear magnetic
resonance (NMR) spectra of replicate samples was obtained. From the ultracentrifugation reference data and the NMR spectra,
an interval partial least-square (iPLS) regression model to predict the amount of cholesterol in the different lipoprotein
fractions was developed. The relative errors of the prediction models were between 12 and 33% and had correlation coefficients
(r) between 0.96 and 0.84. The models were tested with an independent test set giving prediction errors between 19 and 46%
and r between 0.96 and 0.76. Prediction of High, Low and Very Low Density Lipoprotein (HDL, LDL and VLDL) and total cholesterol
was conducted in a study where rats had been supplemented with two doses of air-dried apple-powder. No significant difference
in LDL, VLDL and total cholesterol was observed between the groups. The high apple-powder (20%) group had significantly lower
HDL cholesterol (11%, P = 0.0452) than the control group. It is concluded that the iPLS approach yielded excellent regression models and thus univocal
established chemometric analysis of NMR spectra of rat plasma as a strong and efficient way to quantify lipoprotein fractions
in rat studies. 相似文献
65.
Cecilia Ferndahl Nicklas Bonander Christel Logez Renaud Wagner Lena Gustafsson Christer Larsson Kristina Hedfalk Richard AJ Darby Roslyn M Bill 《Microbial cell factories》2010,9(1):47
Background
Recombinant protein production is universally employed as a solution to obtain the milligram to gram quantities of a given protein required for applications as diverse as structural genomics and biopharmaceutical manufacture. Yeast is a well-established recombinant host cell for these purposes. In this study we wanted to investigate whether our respiratory Saccharomyces cerevisiae strain, TM6*, could be used to enhance the productivity of recombinant proteins over that obtained from corresponding wild type, respiro-fermentative strains when cultured under the same laboratory conditions. 相似文献66.
67.
68.
Reduced baroreflex sensitivity in alcoholic cirrhosis: relations to hemodynamics and humoral systems
Møller S Iversen JS Henriksen JH Bendtsen F 《American journal of physiology. Heart and circulatory physiology》2007,292(6):H2966-H2972
In cirrhosis, arterial vasodilatation leads to central hypovolemia and activation of the sympathetic nervous and renin-angiotensin-aldosterone systems. As the liver disease and circulatory dysfunction may affect baroreflex sensitivity (BRS), we assessed BRS in a large group of patients with cirrhosis and in controls who were all supine and some after 60 degrees passive head-up and 30 degrees head-down tilting in relation to central hemodynamics and activity of the sympathetic nervous and renin-angiotensin-aldosterone systems. One-hundred and five patients (Child classes A/B/C: 21/55/29) and 25 (n=11 + 14) controls underwent a full hemodynamic investigation. BRS was assessed by cross-spectral analysis of variabilities between blood pressure and heart rate time series. The median BRS was significantly lower in the supine cirrhotic patients, 3.7 (range 0.3-30.7) ms/mmHg than in matched controls (n=11): 14.3 (6.1-23.6) ms/mmHg, P<0.001. A stepwise multiple-regression analysis revealed that serum sodium (P=0.044), heart rate (P=0.027), and central circulation time (P=0.034) independently correlated with BRS. Head-down tilting had no effects on BRS, but, after head-up tilting, BRS was similar in the patients (n=23) and controls (n=14). In conclusion, BRS is reduced in cirrhosis in the supine position and relates to various aspects of cardiovascular dysfunction, but no further reduction was observed in parallel with the amelioration of the hyperdynamic circulation after head-up tilting. The results indicate that liver dysfunction and compensatory mechanisms to vasodilatation may be involved in the low BRS, which may contribute to poor cardiovascular adaptation in cirrhosis. 相似文献
69.
Wang L Surendran S Michals-Matalon K Bhatia G Tanskley S Koch R Grady J Tyring SK Stevens RC Guttler F Matalon R 《Genetic testing》2007,11(2):174-178
Tetrahydrobiopterin (BH4) is a co-factor that enhances the activity of other enzymes, and this co-factor level is found to be affected in phenylketonuria (PKU), an amino acid metabolism disorder. The present study was aimed at understanding the effect of BH4 on mutations in the regulatory domain of phenylalanine hydroxylase (PAH). Among 14 patients, 5 patients were classical PKU, 3 were atypical PKU, and 6 were mild PKU. All of these patients had at least one mutation in the regulatory domain. Patients were given 10 mg/kg BH4, and the response of blood phenylalanine (Phe) levels was monitored following treatment. The level of blood Phe decreased after BH4 treatment in all of the patients. These studies suggest that mutations in the regulatory domain also responded to BH4 even if the patient had classical PKU. 相似文献
70.
Lundström P Teilum K Carstensen T Bezsonova I Wiesner S Hansen DF Religa TL Akke M Kay LE 《Journal of biomolecular NMR》2007,38(3):199-212
A simple labeling approach is presented based on protein expression in [1-13C]- or [2-13C]-glucose containing media that produces molecules enriched at methyl carbon positions or backbone Cα sites, respectively. All of the methyl groups, with the exception of Thr and Ile(δ1) are produced with isolated 13C spins (i.e., no 13C–13C one bond couplings), facilitating studies of dynamics through the use of spin-spin relaxation experiments without artifacts
introduced by evolution due to large homonuclear scalar couplings. Carbon-α sites are labeled without concomitant labeling
at Cβ positions for 17 of the common 20 amino acids and there are no cases for which 13Cα−13CO spin pairs are observed. A large number of probes are thus available for the study of protein dynamics with the results
obtained complimenting those from more traditional backbone 15N studies. The utility of the labeling is established by recording 13C R
1ρ and CPMG-based experiments on a number of different protein systems. 相似文献