全文获取类型
收费全文 | 1609篇 |
免费 | 127篇 |
国内免费 | 1篇 |
出版年
2023年 | 6篇 |
2022年 | 7篇 |
2021年 | 32篇 |
2020年 | 20篇 |
2019年 | 27篇 |
2018年 | 20篇 |
2017年 | 26篇 |
2016年 | 42篇 |
2015年 | 68篇 |
2014年 | 55篇 |
2013年 | 120篇 |
2012年 | 118篇 |
2011年 | 127篇 |
2010年 | 99篇 |
2009年 | 90篇 |
2008年 | 123篇 |
2007年 | 90篇 |
2006年 | 87篇 |
2005年 | 93篇 |
2004年 | 99篇 |
2003年 | 96篇 |
2002年 | 101篇 |
2001年 | 18篇 |
2000年 | 15篇 |
1999年 | 21篇 |
1998年 | 17篇 |
1997年 | 12篇 |
1996年 | 15篇 |
1995年 | 15篇 |
1994年 | 10篇 |
1993年 | 10篇 |
1992年 | 14篇 |
1991年 | 2篇 |
1990年 | 2篇 |
1989年 | 11篇 |
1988年 | 6篇 |
1987年 | 4篇 |
1986年 | 2篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1981年 | 4篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1975年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有1737条查询结果,搜索用时 640 毫秒
141.
A new fast method for identification and characterization of proteolytic digests of proteins by monolithic liquid chromatography coupled with mass spectrometry has been developed. The advantages of the monolithic columns are a high-pressure stability and low back pressure resulting in higher flow rates for capillary or nanosize columns simplifying the system handling. As was shown in several publications, such monolithic stationary phases are highly qualified for the analysis of peptides and proteins, but so far, only small volumes could be injected into the system, which might hamper the sample preparation leading to protein precipitation and partial loss of sample. To overcome the problem of small injection volumes, we established a system including a short monolithic trap column to allow preconcentration of the peptides. The injected sample is flushed at higher flow rates onto the trap column, bound to the stationary phase, and in this way concentrated in a few nanoliters before starting the separation. The expanded system was optimized and tested using different reference protein samples. Eluting peptides were detected by MALDI-TOF/TOF-MS and identified by database searching. The system is now a permanent part for proteome analysis in our lab, and as such, it was successfully applied for the detection of post-translational modifications and the analysis of membrane proteins. One example for these analyses is also included in this paper. 相似文献
142.
Heike I. Rsner Martina Caldarini Gregory Potel Daniel Malmodin Maria A. Vanoni Alessandro Aliverti Ricardo A. Broglia Birthe B. Kragelund Guido Tiana 《Proteins》2022,90(1):96-109
The denatured state of several proteins has been shown to display transient structures that are relevant for folding, stability, and aggregation. To detect them by nuclear magnetic resonance (NMR) spectroscopy, the denatured state must be stabilized by chemical agents or changes in temperature. This makes the environment different from that experienced in biologically relevant processes. Using high-resolution heteronuclear NMR spectroscopy, we have characterized several denatured states of a monomeric variant of HIV-1 protease, which is natively structured in water, induced by different concentrations of urea, guanidinium chloride, and acetic acid. We have extrapolated the chemical shifts and the relaxation parameters to the denaturant-free denatured state at native conditions, showing that they converge to the same values. Subsequently, we characterized the conformational properties of this biologically relevant denatured state under native conditions by advanced molecular dynamics simulations and validated the results by comparison to experimental data. We show that the denatured state of HIV-1 protease under native conditions displays rich patterns of transient native and non-native structures, which could be of relevance to its guidance through a complex folding process. 相似文献
143.
144.
Adaptive radiations in butterflies: evolutionary history of the genus Erebia (Nymphalidae: Satyrinae) 下载免费PDF全文
Carlos Peña Heike Witthauer Irena Klečková Zdeněk Fric Niklas Wahlberg 《Biological journal of the Linnean Society. Linnean Society of London》2015,116(2):449-467
We studied the speciose butterfly genus Erebia by reconstructing its phylogenetic relationships using parsimony and Bayesian approaches. We estimated times and rates of diversification for its lineages and employed a biogeographical analysis in order to reconstruct its evolutionary history. DNA sequence data from one mitochondrial gene and three nuclear genes were analyzed for a total of 74 species in Erebia. The estimated dates of origin and diversification for clades, in combination with a biogeographical analysis, suggest that the genus originated in Asian Russia and started its diversification process around 23 Myr. An important event was the dispersal of a lineage from Asia to Western Europe between 23 and 17 Myr, which allowed the radiation of most of species in the genus. The diversification pattern is consistent with a model of diversity limited by clade richness, which implies an early rapid diversification followed by deceleration due to a decrease in speciation. We argue that these characteristics of the evolutionary history of Erebia are consistent with a density‐dependent scenario, with species radiation limited by filling of niche space and reduced resources. We found that the Boeberia parmenio appears strongly supported in the genus Erebia and therefore we place Boeberia Prout, 1901 as a junior synonym of Erebia Dalman, 1816 ( syn. nov. ). 相似文献
145.
Rachid Karam Chih-Hong Lou Heike Kroeger Lulu Huang Jonathan H Lin Miles F Wilkinson 《EMBO reports》2015,16(5):599-609
Endoplasmic reticulum (ER) stress induces the unfolded protein response (UPR), an essential adaptive intracellular pathway that relieves the stress. Although the UPR is an evolutionarily conserved and beneficial pathway, its chronic activation contributes to the pathogenesis of a wide variety of human disorders. The fidelity of UPR activation must thus be tightly regulated to prevent inappropriate signaling. The nonsense-mediated RNA decay (NMD) pathway has long been known to function in RNA quality control, rapidly degrading aberrant mRNAs, and has been suggested to regulate subsets of normal mRNAs. Here, we report that the NMD pathway regulates the UPR. NMD increases the threshold for triggering the UPR in vitro and in vivo, thereby preventing UPR activation in response to normally innocuous levels of ER stress. NMD also promotes the timely termination of the UPR. We demonstrate that NMD directly targets the mRNAs encoding several UPR components, including the highly conserved UPR sensor, IRE1α, whose NMD-dependent degradation partly underpins this process. Our work not only sheds light on UPR regulation, but demonstrates the physiological relevance of NMD''s ability to regulate normal mRNAs. 相似文献
146.
147.
Kristina Vth Carsten Mattes John Reinhard Roberto Covino Heike Stumpf Gerhard Hummer Robert Ernst 《The Journal of cell biology》2021,220(8)
The ER is a key organelle of membrane biogenesis and crucial for the folding of both membrane and secretory proteins. Sensors of the unfolded protein response (UPR) monitor the unfolded protein load in the ER and convey effector functions for maintaining ER homeostasis. Aberrant compositions of the ER membrane, referred to as lipid bilayer stress, are equally potent activators of the UPR. How the distinct signals from lipid bilayer stress and unfolded proteins are processed by the conserved UPR transducer Ire1 remains unknown. Here, we have generated a functional, cysteine-less variant of Ire1 and performed systematic cysteine cross-linking experiments in native membranes to establish its transmembrane architecture in signaling-active clusters. We show that the transmembrane helices of two neighboring Ire1 molecules adopt an X-shaped configuration independent of the primary cause for ER stress. This suggests that different forms of stress converge in a common, signaling-active transmembrane architecture of Ire1. 相似文献
148.
Biotas from all ecosystems need to respond to factors that determine habitat suitability. These factors originate from different
scales. Effects can be assumed to be hierarchical in the order large-scale geographic > regional > local > small-scale in-habitat
factors. We aimed at the identification of general patterns by comparisons between ecosystems (forest floor snails, hololimnic
stream macroinvertebrates) and across scales, and include potential seasonal effects. Sampling sites displayed signs of naturalness,
such as high levels of deadwood accumulation in the forests, or a lack of artificial stream bed fixation plus a “good” to
“high” score for the assemblage-derived Multimetric Index (MMI) in the streams. Terrestrial and aquatic assemblages of non-emergent
taxa fluctuated independent of seasonal effects. They differed in their relative correlation with environmental matrices with
quasi-concentric effects in forests, and longitudinal effects in streams. Large-scale factors, namely geographic position,
strongly influenced assemblage turnover, but the effect is based on a high covariation between geographic position and environmental
factors. We thus extracted variables that best explained species turnover after correcting for spatio-temporal effects. The
terrestrial community assembling was habitat-based and mainly responded to soil acidification, distance to disturbances, and
regional scale deforestation and deciduous/mixed forest cover. The stream assemblages were structured by regional pasture
cover, organic pollution, regional deciduous forest cover and microlithal cover. Apparently, community assembly occurs along
with changes in regional forest cover and the transport of nutrients and matter that can originate from a distance, irrespective
of ecosystem and assumed “naturalness”. 相似文献
149.
The exosome is a conserved protein complex that is responsible for essential 3'→5' RNA degradation in both the nucleus and the cytosol. It is composed of a nine-subunit core complex to which co-factors confer both RNA substrate recognition and ribonucleolytic activities. Very few exosome co-factors have been identified in plants. Here, we have characterized a putative RNA helicase, AtMTR4, that is involved in the degradation of several nucleolar exosome substrates in Arabidopsis thaliana. We show that AtMTR4, rather than its closely related protein HEN2, is required for proper rRNA biogenesis in Arabidopsis. AtMTR4 is mostly localized in the nucleolus, a subcellular compartmentalization that is shared with another exosome co-factor, RRP6L2. AtMTR4 and RRP6L2 cooperate in several steps of rRNA maturation and surveillance, such as processing the 5.8S rRNA and removal of rRNA maturation by-products. Interestingly, degradation of the Arabidopsis 5' external transcribed spacer (5' ETS) requires cooperation of both the 5'→3' and 3'→5' exoribonucleolytic pathways. Accumulating AtMTR4 targets give rise to illegitimate small RNAs; however, these do not affect rRNA metabolism or contribute to the phenotype of mtr4 mutants. Plants lacking AtMTR4 are viable but show several developmental defects, including aberrant vein patterning and pointed first leaves. The mtr4 phenotype resembles that of several ribosomal protein and nucleolin mutants, and may be explained by delayed ribosome biogenesis, as we observed a reduced rate of rRNA accumulation in mtr4 mutants. Taken together, these data link AtMTR4 with rRNA biogenesis and development in Arabidopsis. 相似文献
150.
Clemens G. Borkenstein Josef Knoblechner Heike Frühwirth Michael Schagerl 《Journal of applied phycology》2011,23(1):131-135
The present study reviews the options of cultivating the green alga, Chlorella emersonii, under photoautotrophic conditions with flue gas derived from a cement plant. It was conducted in the Lafarge Perlmooser
plant in Retznei, Austria, where stone coal and various surrogate fuels such as used tyres, plastics and meat-and-bone meal
are incinerated for heating limestone. During 30 days of cultivation, flue gas had no visible adverse effects compared to
the controls grown with pure CO2. The semi-continuous cultivation with media recycling was performed in 5.5-L pH-stat photobioreactors. The essay using CO2 from flue gas yielded a total of 2.00 g L−1 microalgal dry mass and a CO2 fixation of 3.25 g L−1. In the control, a total of 2.06 g L−1 dry mass was produced and 3.38 g L−1 CO2 was fixed. Mean growth rates were between 0.10 day−1 (control) and 0.13 day−1 (flue gas). No accumulation of flue gas residues was detected in the culture medium. At the end of the experiment, however,
the concentration of lead was three times higher in algal biomass compared to the control, indicating that cultures aerated
with this type of flue gas should not be used as food supplements or animal feed. 相似文献