全文获取类型
收费全文 | 5276篇 |
免费 | 469篇 |
国内免费 | 3篇 |
专业分类
5748篇 |
出版年
2024年 | 4篇 |
2023年 | 24篇 |
2022年 | 53篇 |
2021年 | 101篇 |
2020年 | 66篇 |
2019年 | 51篇 |
2018年 | 77篇 |
2017年 | 69篇 |
2016年 | 126篇 |
2015年 | 237篇 |
2014年 | 275篇 |
2013年 | 350篇 |
2012年 | 433篇 |
2011年 | 435篇 |
2010年 | 283篇 |
2009年 | 267篇 |
2008年 | 335篇 |
2007年 | 354篇 |
2006年 | 355篇 |
2005年 | 348篇 |
2004年 | 305篇 |
2003年 | 338篇 |
2002年 | 298篇 |
2001年 | 50篇 |
2000年 | 33篇 |
1999年 | 56篇 |
1998年 | 71篇 |
1997年 | 45篇 |
1996年 | 43篇 |
1995年 | 32篇 |
1994年 | 34篇 |
1993年 | 29篇 |
1992年 | 26篇 |
1991年 | 21篇 |
1990年 | 15篇 |
1989年 | 14篇 |
1988年 | 6篇 |
1987年 | 11篇 |
1986年 | 12篇 |
1985年 | 10篇 |
1984年 | 9篇 |
1983年 | 3篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1979年 | 6篇 |
1978年 | 7篇 |
1977年 | 2篇 |
1974年 | 4篇 |
1973年 | 5篇 |
1969年 | 2篇 |
排序方式: 共有5748条查询结果,搜索用时 14 毫秒
131.
Anita Shepherd Danny Awty-Carroll Jason Kam Chris Ashman Elena Magenau Enrico Martani Mislav Kontek Andrea Ferrarini Stefano Amaducci Chris Davey Vanja Jurišić Gert-Jan Petrie Mohamad Al Hassan Isabelle Lamy Iris Lewandowski Emmanuel de Maupeou Jon McCalmont Luisa Trindade Kasper van der Cruijsen Philip van der Pluijm Rebecca Rowe Andrew Lovett Iain Donnison Andreas Kiesel John Clifton-Brown Astley Hastings 《Global Change Biology Bioenergy》2023,15(4):444-461
New biomass crop hybrids for bioeconomic expansion require yield projections to determine their potential for strategic land use planning in the face of global challenges. Our biomass growth simulation incorporates radiation interception and conversion efficiency. Models often use leaf area to predict interception which is demanding to determine accurately, so instead we use low-cost rapid light interception measurements using a simple laboratory-made line ceptometer and relate the dynamics of canopy closure to thermal time, and to measurements of biomass. We apply the model to project the European biomass potentials of new market-ready hybrids for 2020–2030. Field measurements are easier to collect, the calibration is seasonally dynamic and reduces influence of weather variation between field sites. The model obtained is conservative, being calibrated by crops of varying establishment and varying maturity on less productive (marginal) land. This results in conservative projections of miscanthus hybrids for 2020–2030 based on 10% land use conversion of the least (productive) grassland and arable for farm diversification, which show a European potential of 80.7–89.7 Mt year−1 biomass, with potential for 1.2–1.3 EJ year−1 energy and 36.3–40.3 Mt year−1 carbon capture, with seeded Miscanthus sacchariflorus × sinensis displaying highest yield potential. Simulated biomass projections must be viewed in light of the field measurements on less productive land with high soil water deficits. We are attempting to model the results from an ambitious and novel project combining new hybrids across Europe with agronomy which has not been perfected on less productive sites. Nevertheless, at the time of energy sourcing issues, seed-propagated miscanthus hybrids for the upscaled provision of bioenergy offer an alternative source of renewable energy. If European countries provide incentives for growers to invest, seeded hybrids can improve product availability and biomass yields over the current commercial miscanthus variety. 相似文献
132.
Trémillon N Morello E Llull D Mazmouz R Gratadoux JJ Guillot A Chapot-Chartier MP Monlezun L Solé V Ginisty H Poquet I 《PloS one》2012,7(3):e33516
Background
Protein folding in the envelope is a crucial limiting step of protein export and secretion. In order to better understand this process in Lactococcus lactis, a lactic acid bacterium, genes encoding putative exported folding factors like Peptidyl Prolyl Isomerases (PPIases) were searched for in lactococcal genomes.Results
In L. lactis, a new putative membrane PPIase of the cyclophilin subfamily, PpiA, was identified and characterized. ppiA gene was found to be constitutively expressed under normal and stress (heat shock, H2O2) conditions. Under normal conditions, PpiA protein was synthesized and released from intact cells by an exogenously added protease, showing that it was exposed at the cell surface. No obvious phenotype could be associated to a ppiA mutant strain under several laboratory conditions including stress conditions, except a very low sensitivity to H2O2. Induction of a ppiA copy provided in trans had no effect i) on the thermosensitivity of an mutant strain deficient for the lactococcal surface protease HtrA and ii) on the secretion and stability on four exported proteins (a highly degraded hybrid protein and three heterologous secreted proteins) in an otherwise wild-type strain background. However, a recombinant soluble form of PpiA that had been produced and secreted in L. lactis and purified from a culture supernatant displayed both PPIase and chaperone activities.Conclusions
Although L. lactis PpiA, a protein produced and exposed at the cell surface under normal conditions, displayed a very moderate role in vivo, it was found, as a recombinant soluble form, to be endowed with folding activities in vitro. 相似文献133.
Roselyne Ferrari Isabelle Lacaze Pauline Le Faouder Justine Bertrand-Michel Camille Oger Jean-Marie Galano Thierry Durand Stéphane Moularat Laetitia Chan Ho Tong Charlie Boucher Jaafar Kilani Yohann Petit Océane Vanparis César Trannoy Sylvain Brun Hervé Lalucque Fabienne Malagnac Philippe Silar 《Biochimica et Biophysica Acta (BBA)/General Subjects》2018,1862(10):2174-2182
Oxylipins are secondary messengers used universally in the living world for communication and defense. The paradigm is that they are produced enzymatically for the eicosanoids and non-enzymatically for the isoprostanoids. They are supposed to be degraded into volatile organic compounds (VOCs) and to participate in aroma production. Some such chemicals composed of eight carbons are also envisoned as alternatives to fossil fuels. In fungi, oxylipins have been mostly studied in Aspergilli and shown to be involved in signalling asexual versus sexual development, mycotoxin production and interaction with the host for pathogenic species. Through targeted gene deletions of genes encoding oxylipin-producing enzymes and chemical analysis of oxylipins and volatile organic compounds, we show that in the distantly-related ascomycete Podospora anserina, isoprostanoids are likely produced enzymatically. We show the disappearance in the mutants lacking lipoxygenases and cyclooxygenases of the production of 10-hydroxy-octadecadienoic acid and that of 1-octen-3-ol, a common volatile compound. Importantly, this was correlated with the inability of the mutants to repel nematodes as efficiently as the wild type. Overall, our data show that in this fungus, oxylipins are not involved in signalling development but may rather be used directly or as precursors in the production of odors against potential agressors.
Significance
We analyzse the role in inter-kingdom communication of lipoxygenase (lox) and cyclooxygenase (cox) genes in the model fungus Podospora anserina.Through chemical analysis we define the oxylipins and volatile organic compounds (VOCs)produce by wild type and mutants for cox and lox genes,We show that the COX and LOX genes are required for the production of some eight carbon VOCs.We show that COX and LOX genes are involved in the production of chemicals repelling nematodes.This role is very different from the ones previously evidenced in other fungi. 相似文献134.
Carrière Audrey Lagarde Damien Jeanson Yannick Portais Jean-Charles Galinier Anne Ader Isabelle Casteilla Louis 《Journal of physiology and biochemistry》2020,76(2):241-250
Journal of Physiology and Biochemistry - Thermogenic (brown and beige) adipose tissues improve glucose and lipid homeostasis and therefore represent putative targets to cure obesity and related... 相似文献
135.
The voltage-dependent anion channel (VDAC) is a critical β-barrel membrane protein of the mitochondrial outer membrane, which regulates the transport of ions and ATP between mitochondria and the cytoplasm. In addition, VDAC plays a central role in the control of apoptosis and is therefore of great interest in both cancer and neurodegenerative diseases. Although not fully understood, it is presumed that the gating mechanism of VDAC is governed by its N-terminal region which, in the open state of the channel, exhibits an α-helical structure positioned midway inside the pore and strongly interacting with the β-barrel wall. In the present work, we performed molecular simulations with a recently developed force field for disordered systems to shed new light on known experimental results, showing that the N-terminus of VDAC is an intrinsically disordered region (IDR). First, simulation of the N-terminal segment as a free peptide highlighted its disordered nature and the importance of using an IDR-specific force field to properly sample its conformational landscape. Secondly, accelerated dynamics simulation of a double cysteine VDAC mutant under applied voltage revealed metastable low conducting states of the channel representative of closed states observed experimentally. Related structures were characterized by partial unfolding and rearrangement of the N-terminal tail, that led to steric hindrance of the pore. Our results indicate that the disordered properties of the N-terminus are crucial to properly account for the gating mechanism of VDAC. 相似文献
136.
Isabelle Defourny Andrea Minetti Géza Harczi Stéphane Doyon Susan Shepherd Milton Tectonidis Jean-Hervé Bradol Michael Golden 《PloS one》2009,4(5)
Background
There are 146 million underweight children in the developing world, which contribute to up to half of the world''s child deaths. In high burden regions for malnutrition, the treatment of individual children is limited by available resources. Here, we evaluate a large-scale distribution of a nutritional supplement on the prevention of wasting.Methods and Findings
A new ready-to-use food (RUF) was developed as a diet supplement for children under three. The intervention consisted of six monthly distributions of RUF during the 2007 hunger gap in a district of Maradi region, Niger, for approximately 60,000 children (length: 60–85 cm). At each distribution, all children over 65 cm had their Mid-Upper Arm Circumference (MUAC) recorded. Admission trends for severe wasting (WFH<70% NCHS) in Maradi, 2002–2005 show an increase every year during the hunger gap. In contrast, in 2007, throughout the period of the distribution, the incidence of severe acute malnutrition (MUAC<110 mm) remained at extremely low levels. Comparison of year-over-year admissions to the therapeutic feeding program shows that the 2007 blanket distribution had essentially the same flattening effect on the seasonal rise in admissions as the 2006 individualized treatment of almost 60,000 children moderately wasted.Conclusions
These results demonstrate the potential for distribution of fortified spreads to reduce the incidence of severe wasting in large population of children 6–36 months of age. Although further information is needed on the cost-effectiveness of such distributions, these results highlight the importance of re-evaluating current nutritional strategies and international recommendations for high burden areas of childhood malnutrition. 相似文献137.
Formyl peptide receptors: a promiscuous subfamily of G protein-coupled receptors controlling immune responses 总被引:3,自引:0,他引:3
The formyl peptide receptor (FPR) family is involved in host defence against pathogens, but also in sensing internal molecules that may constitute signals of cellular dysfunction. It includes three subtypes in human and other primates. FPR responds to formyl peptides derived from bacterial and mitochondrial proteins. FPRL1 displays a large array of exogenous and endogenous ligands, including the chemokine variant sCKβ8-1, the neuroprotective peptide humanin, and lipoxin A4. Two high affinity agonists (F2L and humanin) were recently described for FPRL2. In mouse, eight FPR-related receptors have been described. Fpr1 is the ortholog of human FPR, while fpr2 appears to share many ligands with human FPRL1. Altogether, the physiological role of the FPR family is still incompletely understood, due in part to the large variety of ligands, the redundancy with other chemoattractant agents, and the lack of clear orthologs between human and mouse receptors. Newly developed tools will allow to study further this family of receptors. 相似文献
138.
Comparative proteome profiling and functional analysis of chronic myelogenous leukemia cell lines 总被引:1,自引:0,他引:1
Fontana S Alessandro R Barranca M Giordano M Corrado C Zanella-Cleon I Becchi M Kohn EC De Leo G 《Journal of proteome research》2007,6(11):4330-4342
The aim of the present study was the molecular profiling of different Ph+ chronic myelogenous leukemia (CML) cell lines (LAMA84, K562, and KCL22) by a proteomic approach. By employing two-dimensional gel electrophoresis combined with mass spectrometry analysis, we have identified 191 protein spots corresponding to 142 different proteins. Among these, 63% were cancer-related proteins and 74% were described for the first time in leukemia cells. Multivariate analysis highlighted significant differences in the global proteomic profile of the three CML cell lines. In particular, the detailed analysis of 35 differentially expressed proteins revealed that LAMA84 cells preferentially expressed proteins associated with an invasive behavior, while K562 and KCL22 cells preferentially expressed proteins involved in drug resistance. These data demonstrate that these CML cell lines, although representing the same pathological phenotype, show characteristics in their protein expression profile that suggest different phenotypic leukemia subclasses. These data contribute a new potential characterization of the CML phenotype and may help to understand interpatient variability in the progression of disease and in the efficacy of a treatment. 相似文献
139.
Lancelot N Charier G Couprie J Duband-Goulet I Alpha-Bazin B Quémeneur E Ma E Marsolier-Kergoat MC Ropars V Charbonnier JB Miron S Craescu CT Callebaut I Gilquin B Zinn-Justin S 《Nucleic acids research》2007,35(17):5898-5912
DNA damage checkpoints are signal transduction pathways that are activated after genotoxic insults to protect genomic integrity. At the site of DNA damage, ‘mediator’ proteins are in charge of recruiting ‘signal transducers’ to molecules ‘sensing’ the damage. Budding yeast Rad9, fission yeast Crb2 and metazoan 53BP1 are presented as mediators involved in the activation of checkpoint kinases. Here we show that, despite low sequence conservation, Rad9 exhibits a tandem tudor domain structurally close to those found in human/mouse 53BP1 and fission yeast Crb2. Moreover, this region is important for the resistance of Saccharomyces cerevisiae to different genotoxic stresses. It does not mediate direct binding to a histone H3 peptide dimethylated on K79, nor to a histone H4 peptide dimethylated on lysine 20, as was demonstrated for 53BP1. However, the tandem tudor region of Rad9 directly interacts with single-stranded DNA and double-stranded DNAs of various lengths and sequences through a positively charged region absent from 53BP1 and Crb2 but present in several yeast Rad9 homologs. Our results argue that the tandem tudor domains of Rad9, Crb2 and 53BP1 mediate chromatin binding next to double-strand breaks. However, their modes of chromatin recognition are different, suggesting that the corresponding interactions are differently regulated. 相似文献
140.
Buache E Garnotel R Aubert D Gillery P Villena I 《Biochemical and biophysical research communications》2007,359(2):298-303
The apicomplexan Toxoplasma gondii, an obligate intracellular parasite, can infect humans and a wide range of vertebrates. Following oral infection, the parasite invades tissues by crossing non-permissive biological barriers such as the placenta or the blood-brain barrier. But the molecular mechanisms underlying migration of T. gondii remain poorly characterized. The crossing of various basal membranes and infiltration into the extracellular matrix by T. gondii could involve matrix metalloproteinases (MMPs). We demonstrated a decrease in proMMP-2 and proMMP-9 secretion by THP-1 cells at 24 and 48h post invasion with regulation at the mRNA level throughout infection. This down regulation was associated with a decrease in TIMP-2 secretion and an inhibition of its expression. Moreover, results showed an activation of MT1-MMP; its expression was regulated after 6, 24, and 48h. 相似文献