全文获取类型
收费全文 | 534篇 |
免费 | 43篇 |
出版年
2022年 | 13篇 |
2021年 | 16篇 |
2020年 | 10篇 |
2019年 | 12篇 |
2018年 | 14篇 |
2017年 | 16篇 |
2016年 | 12篇 |
2015年 | 23篇 |
2014年 | 35篇 |
2013年 | 37篇 |
2012年 | 55篇 |
2011年 | 41篇 |
2010年 | 26篇 |
2009年 | 25篇 |
2008年 | 26篇 |
2007年 | 35篇 |
2006年 | 25篇 |
2005年 | 29篇 |
2004年 | 21篇 |
2003年 | 15篇 |
2002年 | 12篇 |
2001年 | 12篇 |
2000年 | 12篇 |
1999年 | 9篇 |
1998年 | 1篇 |
1997年 | 4篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 3篇 |
1993年 | 1篇 |
1991年 | 2篇 |
1990年 | 5篇 |
1989年 | 5篇 |
1988年 | 2篇 |
1987年 | 1篇 |
1986年 | 2篇 |
1984年 | 3篇 |
1983年 | 3篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 3篇 |
1979年 | 1篇 |
1978年 | 2篇 |
1973年 | 1篇 |
排序方式: 共有577条查询结果,搜索用时 31 毫秒
101.
Raphy Zarecki Matthew A. Oberhardt Keren Yizhak Allon Wagner Ella Shtifman Segal Shiri Freilich Christopher S. Henry Uri Gophna Eytan Ruppin 《PloS one》2014,9(5)
Growth rate has long been considered one of the most valuable phenotypes that can be measured in cells. Aside from being highly accessible and informative in laboratory cultures, maximal growth rate is often a prime determinant of cellular fitness, and predicting phenotypes that underlie fitness is key to both understanding and manipulating life. Despite this, current methods for predicting microbial fitness typically focus on yields [e.g., predictions of biomass yield using GEnome-scale metabolic Models (GEMs)] or notably require many empirical kinetic constants or substrate uptake rates, which render these methods ineffective in cases where fitness derives most directly from growth rate. Here we present a new method for predicting cellular growth rate, termed SUMEX, which does not require any empirical variables apart from a metabolic network (i.e., a GEM) and the growth medium. SUMEX is calculated by maximizing the SUM of molar EXchange fluxes (hence SUMEX) in a genome-scale metabolic model. SUMEX successfully predicts relative microbial growth rates across species, environments, and genetic conditions, outperforming traditional cellular objectives (most notably, the convention assuming biomass maximization). The success of SUMEX suggests that the ability of a cell to catabolize substrates and produce a strong proton gradient enables fast cell growth. Easily applicable heuristics for predicting growth rate, such as what we demonstrate with SUMEX, may contribute to numerous medical and biotechnological goals, ranging from the engineering of faster-growing industrial strains, modeling of mixed ecological communities, and the inhibition of cancer growth. 相似文献
102.
Rinat Sharir Jonathan Semo Sara Shimoni Tamar Ben-Mordechai Natalie Landa-Rouben Sofia Maysel-Auslender Aviv Shaish Michal Entin–Meer Gad Keren Jacob George 《PloS one》2014,9(12)
Background
Ischemic cardiac damage is associated with upregulation of cardiac pro-inflammatory cytokines, as well as invasion of lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We sought to determine whether the Treg pool is influenced by myocardial damage and whether Tregs transfer and deletion affect cardiac remodeling.Methods and Results
The number and functional suppressive activity of Tregs were assayed in mice subjected to experimental myocardial infarction. The numbers of splenocyte-derived Tregs in the ischemic mice were significantly higher after the injury than in the controls, and their suppressive properties were significantly compromised. Compared with PBS, adoptive Treg transfer to mice with experimental infarction reduced infarct size and improved LV remodeling and functional performance by echocardiography. Treg deletion with blocking anti-CD25 antibodies did not influence infarct size or echocardiographic features of cardiac remodeling.Conclusion
Treg numbers are increased whereas their function is compromised in mice with that underwent experimental infarction. Transfer of exogeneous Tregs results in attenuation of myocardial remodeling whereas their ablation has no effect. Thus, Tregs may serve as interesting potential interventional targets for attenuating left ventricular remodeling. 相似文献103.
In a foraging game, predators must catch elusive prey while avoiding injury. Predators manage their hunting success with behavioral tools such as habitat selection, time allocation, and perhaps daring—the willingness to risk injury to increase hunting success. A predator’s level of daring should be state dependent: the hungrier it is, the more it should be willing to risk injury to better capture prey. We ask, in a foraging game, will a hungry predator be more willing to risk injury while hunting? We performed an experiment in an outdoor vivarium in which barn owls (Tyto alba) were allowed to hunt Allenby’s gerbils (Gerbillus andersoni allenbyi) from a choice of safe and risky patches. Owls were either well fed or hungry, representing the high and low state, respectively. We quantified the owls’ patch use behavior. We predicted that hungry owls would be more daring and allocate more time to the risky patches. Owls preferred to hunt in the safe patches. This indicates that owls manage risk of injury by avoiding the risky patches. Hungry owls doubled their attacks on gerbils, but directed the added effort mostly toward the safe patch and the safer, open areas in the risky patch. Thus, owls dared by performing a risky action—the attack maneuver—more times, but only in the safest places—the open areas. We conclude that daring can be used to manage risk of injury and owls implement it strategically, in ways we did not foresee, to minimize risk of injury while maximizing hunting success. 相似文献
104.
Shahar Rotem-Bamberger Jamal Fahoum Keren Keinan-Adamsky Tomer Tsaban Orly Avraham Deborah E. Shalev Jordan H. Chill Ora Schueler-Furman 《The Journal of biological chemistry》2022,298(8)
Class I WW domains are present in many proteins of various functions and mediate protein interactions by binding to short linear PPxY motifs. Tandem WW domains often bind peptides with multiple PPxY motifs, but the interplay of WW–peptide interactions is not always intuitive. The WW domain–containing oxidoreductase (WWOX) harbors two WW domains: an unstable WW1 capable of PPxY binding and stable WW2 that cannot bind PPxY. The WW2 domain has been suggested to act as a WW1 domain chaperone, but the underlying mechanism of its chaperone activity remains to be revealed. Here, we combined NMR, isothermal calorimetry, and structural modeling to elucidate the roles of both WW domains in WWOX binding to its PPxY-containing substrate ErbB4. Using NMR, we identified an interaction surface between these two domains that supports a WWOX conformation compatible with peptide substrate binding. Isothermal calorimetry and NMR measurements also indicated that while binding affinity to a single PPxY motif is marginally increased in the presence of WW2, affinity to a dual-motif peptide increases 10-fold. Furthermore, we found WW2 can directly bind double-motif peptides using its canonical binding site. Finally, differential binding of peptides in mutagenesis experiments was consistent with a parallel N- to C-terminal PPxY tandem motif orientation in binding to the WW1–WW2 tandem domain, validating structural models of the interaction. Taken together, our results reveal the complex nature of tandem WW-domain organization and substrate binding, highlighting the contribution of WWOX WW2 to both protein stability and target binding. 相似文献
105.
106.
CYP3A4 is recognized as the main enzyme involved in the metabolism of drugs and xenobiotics in the human body and its inhibition may lead to undesirable consequences. Stilbenes, including resveratrol, belong to a group of dietary health-promoting compounds that also act as inhibitors of CYP3A4. The aim of this study was to examine the use of computer modeling of enzyme-ligand interactions to analyze and predict the inhibition of structurally related compounds. To this end, an aldehyde group was attached to resveratrol and the interactions of CYP3A4 with resveratrol, its aldehyde analogue (RA) and a known synthetic inhibitor were studied and compared in two biological models. Specifically, the metabolism of testosterone was examined in a human intestine cell line (Caco-2/TC7) and in rat liver microsomes (RLM). The results demonstrated a weak inhibitory effect of RA on CYP3A4, as compared to resveratrol itself, in both biological models. Human CYP3A4 was more susceptible to inhibition than the commonly used model isozyme from rat. Modeling of the binding site of CYP3A4 revealed a combination of three types of interactions: hydrophobic interactions, electrostatic interactions and hydrogen bonds. A docking simulation revealed that the RA lacked an important binding feature, as compared to resveratrol, and that that difference may be responsible for its lower level of affinity for CYP3A4. Software analysis of binding affinity may serve as a predictive tool for designing new therapeutic compounds in terms of inhibition of CYP3A4 and help to reveal the biochemical nature of the interactions of dietary compounds, herbal compounds and drugs whose metabolism is mediated by this enzyme. 相似文献
107.
Ten years of MON 810 resistance monitoring of field populations of Ostrinia nubilalis in Europe
下载免费PDF全文
![点击此处可从《Journal of Applied Entomology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
T. G. M. Thieme C. Buuk K. Gloyna F. Ortego G. P. Farinós 《Journal of Applied Entomology》2018,142(1-2):192-200
From 2005 to 2015, Ostrinia nubilalis were collected in the most important maize‐growing areas in Europe where MON 810 was cultivated. The susceptibility of these O. nubilalis collections to the Cry1Ab protein was determined using overlay bioassays and compared to that of reference (control) strains. Larvae that died or did not moult after 7 days were used to calculate a moulting inhibition concentration (MIC). Two different batches of Cry1Ab protein were used over the course of this study. Between 2005 and 2015, 145 collections of O. nubilalis from 14 areas were analysed. The Cry1Ab susceptibility of populations from different geographic regions differed only slightly across years. The greatest variability in the MIC50 for field samples collected from 2005 to 2011 and tested with batch 1 was 6.6‐fold in 2006. For field‐collected O. nubilalis, the difference between MIC50 values of the most susceptible and most tolerant samples was 13.1‐fold for this period. For samples collected in 2012–2015 and tested with batch 2, the greatest variability was 4.1‐fold in 2014. A diagnostic concentration (MIC99) was calculated for batch 1 (48 ng/cm2) using the results from all the collections in 2005–2012. Bridging experiments indicated that the diagnostic concentration for batch 2 was 28 ng/cm2. From 2006 onwards, no O. nubilalis reached the 2nd larval stage when the diagnostic concentration of either batch of Cry1Ab was used. Only one insect collected from Romania in 2012 and two insects collected as reference strain from Spain in 2015 survived exposure to a dosage of 20 ng/cm2, and none of these larvae survived on MON 810 maize. Our results indicate that there has been no significant change in susceptibility to Cry1Ab in European populations of O. nubilalis over the period 2005–2015. 相似文献
108.
René Uebe Noa Keren‐Khadmy Natalie Zeytuni Emanuel Katzmann Yotam Navon Geula Davidov Ronit Bitton Jürgen M. Plitzko Dirk Schüler Raz Zarivach 《Molecular microbiology》2018,107(4):542-557
Magnetospirillum gryphiswaldense MSR‐1 synthesizes membrane‐enclosed magnetite (Fe3O4) nanoparticles, magnetosomes, for magnetotaxis. Formation of these organelles involves a complex process comprising key steps which are governed by specific magnetosome‐associated proteins. MamB, a cation diffusion facilitator (CDF) family member has been implicated in magnetosome‐directed iron transport. However, deletion mutagenesis studies revealed that MamB is essential for the formation of magnetosome membrane vesicles, but its precise role remains elusive. In this study, we employed a multi‐disciplinary approach to define the role of MamB during magnetosome formation. Using site‐directed mutagenesis complemented by structural analyses, fluorescence microscopy and cryo‐electron tomography, we show that MamB is most likely an active magnetosome‐directed transporter serving two distinct, yet essential functions. First, MamB initiates magnetosome vesicle formation in a transport‐independent process, probably by serving as a landmark protein. Second, MamB transport activity is required for magnetite nucleation. Furthermore, by determining the crystal structure of the MamB cytosolic C‐terminal domain, we also provide mechanistic insight into transport regulation. Additionally, we present evidence that magnetosome vesicle growth and chain formation are independent of magnetite nucleation and magnetic interactions respectively. Together, our data provide novel insight into the role of the key bifunctional magnetosome protein MamB, and the early steps of magnetosome formation. 相似文献
109.
N. Kondo Manabu Nakadome Keren Zhang Tomoyuki Shiojiri Manabu Shibasaki Kozo Hirata Atsushi Iwata 《International journal of biometeorology》1997,40(2):99-102
The purpose of this study was to investigate whether there are any effects of skin temperature changes on sweating response
in the first few minutes of mild exercise. Six healthy males performed a bicycle exercise at 100 W (50 rpm) for 30 min under
an ambient temperature of 23° C (40% RH). Esophageal temperature (T
es), mean skin temperature (T–
sk), local skin temperature at the lower left scapula (T
sl), local sweating rate (M.
sw), and cutaneous blood flow by laser-Doppler flowmetry (LDF) were measured continuously. Although T
sl decreased markedly just after the onset of sweating, T–
sk did not change. M.
sw did not increase constantly in the early stages of exercise, and there was a temporary interruption in the increase of M.
sw. This interruption in sweating was affected by the rate of change in T
sl rather than by the absolute value of T
sl, since there was a positive and significant correlation between the time of the interruption in the increase of M.
sw and the rate of decrease in T
sl (y=6.47x+0.04; r=0.86, P<0.05). The results suggest that sweating response in the early stages of exercise may be influenced by changes in local skin
temperature due to evaporative cooling.
Received: 31 August 1995 / Revised: 26 February 1996 / Accepted: 26 July 1996, 相似文献
110.
M.-T. Rofe Y. Shacham A. Steinvi L. Barak M. Hareuveni S. Banai G. Keren A. Finkelstein H. Shmilovich 《Netherlands heart journal》2016,24(5):350-354