全文获取类型
收费全文 | 44518篇 |
免费 | 3477篇 |
国内免费 | 9篇 |
出版年
2023年 | 325篇 |
2022年 | 499篇 |
2021年 | 1013篇 |
2020年 | 773篇 |
2019年 | 955篇 |
2018年 | 1339篇 |
2017年 | 1290篇 |
2016年 | 1623篇 |
2015年 | 1960篇 |
2014年 | 2114篇 |
2013年 | 2975篇 |
2012年 | 3671篇 |
2011年 | 3593篇 |
2010年 | 2160篇 |
2009年 | 1737篇 |
2008年 | 2680篇 |
2007年 | 2595篇 |
2006年 | 2472篇 |
2005年 | 2126篇 |
2004年 | 2070篇 |
2003年 | 1889篇 |
2002年 | 1701篇 |
2001年 | 665篇 |
2000年 | 704篇 |
1999年 | 551篇 |
1998年 | 394篇 |
1997年 | 269篇 |
1996年 | 256篇 |
1995年 | 262篇 |
1994年 | 188篇 |
1993年 | 198篇 |
1992年 | 290篇 |
1991年 | 235篇 |
1990年 | 206篇 |
1989年 | 179篇 |
1988年 | 147篇 |
1987年 | 170篇 |
1986年 | 142篇 |
1985年 | 119篇 |
1984年 | 168篇 |
1983年 | 107篇 |
1982年 | 126篇 |
1981年 | 107篇 |
1980年 | 102篇 |
1979年 | 92篇 |
1978年 | 85篇 |
1977年 | 66篇 |
1976年 | 60篇 |
1975年 | 68篇 |
1974年 | 80篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
991.
María Victoria Martín Ayelén Mariana Distefano Eduardo Julián Zabaleta Gabriela Carolina Pagnussat 《Plant signaling & behavior》2013,8(10)
Previously considered as toxic by-products of aerobic metabolism, reactive oxygen species (ROS) are emerging as essential signaling molecules in eukaryotes. Recent evidence showed that maintenance of ROS homeostasis during female gametophyte development is crucial for embryo sac patterning and fertilization. Although ROS are exclusively detected in the central cell of mature embryo sacs, the study of mutants deficient in ROS homeostasis suggests that controlled oxidative bursts might take place earlier during gametophyte development. Also, a ROS burst that depends on pollination takes place inside the embryo sac. This oxidative response might be required for pollen tube growth arrest and for sperm cell release. In this mini-review, we will focus on new insights into the role of ROS during female gametophyte development and fertilization. Special focus will be made on the mitochondrial Mn-Superoxide dismutase (MSD1), which has been recently reported to be essential for maintaining ROS homeostasis during embryo sac formation. 相似文献
992.
Walid Toujani Jesús Mu?oz-Bertomeu María Flores-Tornero Sara Rosa-Téllez Armand Djoro Anoman Roc Ros 《Plant signaling & behavior》2013,8(11)
Three different pathways of serine (Ser) biosynthesis have been described in plants: the Glycolate pathway, which is part of the Photorespiratory pathway, and 2 non-Photorespiratory pathways, the Glycerate and the Phosphorylated pathways. The Phosphorylated Pathway of Ser Biosynthesis (PPSB) has been known to exist since the 1950s, but its biological relevance was not revealed until quite recently when the last enzyme of the pathway, the Phosphoserine Phosphatase, was functionally characterized. In the associated study1, we characterized a family of genes coding for putatite phosphoglycerate dehydrogenases (PGDH, 3-PGDH, and EDA9), the first enzyme of the PPSB. A metabolomics study using overexpressing plants indicated that all PGDH family genes were able to regulate Ser homeostasis but only lacking of EDA9 expression caused drastic developmental defects. We provided genetic and molecular evidence for the essential role of EDA9 for embryo and pollen development. Here, some new insights into the physiological/molecular function of PPSB and Ser are presented and discussed. 相似文献
993.
François Binet Gaëlle Mawambo Nicholas Sitaras Nicolas Tetreault Eric Lapalme Sandra Favret Agustin Cerani Dominique Leboeuf Sophie Tremblay Flavio Rezende Aimee M. Juan Andreas Stahl Jean-Sebastien Joyal Éric Milot Randal J. Kaufman Martin Guimond Timothy E. Kennedy Przemyslaw Sapieha 《Cell metabolism》2013,17(3):353-371
- Download : Download high-res image (338KB)
- Download : Download full-size image
994.
Kyriakos Kentzoglanakis Diana García López Sam P. Brown Richard A. Goldstein 《PLoS computational biology》2013,9(4)
The repression of competition by mechanisms of policing is now recognized as a major force in the maintenance of cooperation. General models on the evolution of policing have focused on the interplay between individual competitiveness and mutual policing, demonstrating a positive relationship between within-group diversity and levels of policing. We expand this perspective by investigating what is possibly the simplest example of reproductive policing: copy number control (CNC) among non-conjugative plasmids, a class of extra-chromosomal vertically transmitted molecular symbionts of bacteria. Through the formulation and analysis of a multi-scale dynamical model, we show that the establishment of stable reproductive restraint among plasmids requires the co-evolution of two fundamental plasmid traits: policing, through the production of plasmid-coded trans-acting replication inhibitors, and obedience, expressed as the binding affinity of plasmid-specific targets to those inhibitors. We explain the intrinsic replication instabilities that arise in the absence of policing and we show how these instabilities are resolved by the evolution of copy number control. Increasing levels of policing and obedience lead to improvements in group performance due to tighter control of local population size (plasmid copy number), delivering benefits both to plasmids, by reducing the risk of segregational loss and to the plasmid-host partnership, by increasing the rate of cell reproduction, and therefore plasmid vertical transmission. 相似文献
995.
Silvio a Beccara Tatjana ?krbi? Roberto Covino Cristian Micheletti Pietro Faccioli 《PLoS computational biology》2013,9(3)
We report on atomistic simulation of the folding of a natively-knotted protein, MJ0366, based on a realistic force field. To the best of our knowledge this is the first reported effort where a realistic force field is used to investigate the folding pathways of a protein with complex native topology. By using the dominant-reaction pathway scheme we collected about 30 successful folding trajectories for the 82-amino acid long trefoil-knotted protein. Despite the dissimilarity of their initial unfolded configuration, these trajectories reach the natively-knotted state through a remarkably similar succession of steps. In particular it is found that knotting occurs essentially through a threading mechanism, involving the passage of the C-terminal through an open region created by the formation of the native -sheet at an earlier stage. The dominance of the knotting by threading mechanism is not observed in MJ0366 folding simulations using simplified, native-centric models. This points to a previously underappreciated role of concerted amino acid interactions, including non-native ones, in aiding the appropriate order of contact formation to achieve knotting. 相似文献
996.
997.
Environmental strain Burkholderia sp. DNT mineralizes the xenobiotic compound 2,4-dinitrotoluene (DNT) owing to the catabolic dnt genes borne by plasmid DNT, but the process fails to promote significant growth. To investigate this lack of physiological return of such an otherwise complete metabolic route, cells were exposed to DNT under various growth conditions and the endogenous formation of reactive oxygen species (ROS) monitored in single bacteria. These tests revealed the buildup of a strong oxidative stress in the population exposed to DNT. By either curing the DNT plasmid or by overproducing the second activity of the biodegradation route (DntB) we could trace a large share of ROS production to the first reaction of the route, which is executed by the multicomponent dioxygenase encoded by the dntA gene cluster. Naphthalene, the ancestral substrate of the dioxygenase from which DntA has evolved, also caused significant ROS formation. That both the old and the new substrate brought about a considerable cellular stress was indicative of a still-evolving DntA enzyme which is neither optimal any longer for naphthalene nor entirely advantageous yet for growth of the host strain on DNT. We could associate endogenous production of ROS with likely error-prone repair mechanisms of DNA damage, and the ensuing stress-induced mutagenesis in cells exposed to DNT. It is thus plausible that the evolutionary roadmap for biodegradation of xenobiotic compounds like DNT was largely elicited by mutagenic oxidative stress caused by faulty reactions of precursor enzymes with novel but structurally related substrates-to-be. 相似文献
998.
María J. López-Armada Romina R. Riveiro-Naveira Carlos Vaamonde-García Marta N. Valcárcel-Ares 《Mitochondrion》2013,13(2):106-118
Inflammation has been linked to multiple degenerative and acute diseases as well as the aging process. Moreover, mitochondrial alterations play a central role in these processes. Mitochondria have an important role in pro-inflammatory signaling; similarly, pro-inflammatory mediators may also alter mitochondrial function. Both of these processes increase mitochondrial oxidative stress, promoting a vicious inflammatory cycle. Additionally, damage-associated molecular patterns derived from mitochondria could contribute to inflammasome formation and caspase-1 activation, while alterations in mitochondrial autophagy may cause inflammation. Strategies aimed at controlling excessive oxidative stress within mitochondria may represent both preventive and therapeutic interventions in inflammation. 相似文献
999.
Ana C. Silva Sandra Almeida Mário Laço Ana I. Duarte Joana Domingues Catarina R. Oliveira Cristina Januário A. Cristina Rego 《Mitochondrion》2013,13(6):801-809
Mitochondrial dysfunction has been implicated in Huntington's disease (HD) pathogenesis. We analyzed the activity of mitochondrial complexes (Cx) I–IV, protein levels of selected Cx subunits and adenine nucleotides in platelet mitochondria from pre-symptomatic versus symptomatic HD human carriers and age-matched control individuals. Mitochondrial platelets exhibited reduced activity of citrate synthase in pre-symptomatic and Cx-I in pre-symptomatic and symptomatic HD carriers. Positive correlation between Cx activity and protein subunits was observed for Cx-I in symptomatic HD patient's mitochondria. Moreover, AMP increased in mitochondria from pre-symptomatic HD carriers. Results highlight mitochondrial changes occurring before the onset of HD clinical symptoms. 相似文献
1000.
Jorge Almarza Luis Rincón Alí Bahsas María Angela Pinto Francisco Brito 《The protein journal》2013,32(2):118-125
Understanding of protein–urea interactions is one of the greatest challenges to modern structural protein chemistry. Based in enzyme kinetics experiments and 1H NMR spectroscopic analysis we proposed that urea, at low concentrations, directly interacts with the protonated histidines of the active center of RNase A, following a simple model of competitive inhibition. These results were supported by theoretical analysis based on the frontier molecular orbital theory and suggest that urea might establish a favorable interaction with the cationic amino acids. Our experimental evidence and theoretical analysis indicate that the initials steps of the molecular mechanism of Urea–RNase A interaction passes through the establishment of a three center four electron adduct. Also, our results would explain the observed disruption of the 1H NMR signals corresponding to H12 and H119 (involved in catalysis) of the RNase A studied in the presence of urea. Our interaction model of urea–amino acids (cationic) can be extended to explain the inactivation of other enzymes with cationic amino acids at the active site. 相似文献