全文获取类型
收费全文 | 5771篇 |
免费 | 470篇 |
专业分类
6241篇 |
出版年
2023年 | 20篇 |
2022年 | 48篇 |
2021年 | 102篇 |
2020年 | 59篇 |
2019年 | 84篇 |
2018年 | 93篇 |
2017年 | 105篇 |
2016年 | 125篇 |
2015年 | 245篇 |
2014年 | 269篇 |
2013年 | 399篇 |
2012年 | 463篇 |
2011年 | 455篇 |
2010年 | 324篇 |
2009年 | 272篇 |
2008年 | 389篇 |
2007年 | 398篇 |
2006年 | 372篇 |
2005年 | 327篇 |
2004年 | 319篇 |
2003年 | 280篇 |
2002年 | 279篇 |
2001年 | 67篇 |
2000年 | 61篇 |
1999年 | 62篇 |
1998年 | 68篇 |
1997年 | 49篇 |
1996年 | 38篇 |
1995年 | 34篇 |
1994年 | 27篇 |
1993年 | 22篇 |
1992年 | 37篇 |
1991年 | 22篇 |
1990年 | 29篇 |
1989年 | 23篇 |
1988年 | 30篇 |
1987年 | 17篇 |
1986年 | 16篇 |
1985年 | 19篇 |
1984年 | 16篇 |
1983年 | 12篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1979年 | 10篇 |
1978年 | 13篇 |
1977年 | 11篇 |
1975年 | 10篇 |
1974年 | 10篇 |
1973年 | 12篇 |
1966年 | 8篇 |
排序方式: 共有6241条查询结果,搜索用时 15 毫秒
41.
Adaptation to adverse environmental conditions such as high altitude requires physiological and/or morphological changes. Genome scans provide a means to identify the genetic basis of such adaptations without previous knowledge about the particular genetic variants or traits under selection. In this study, we scanned 3027 amplified fragment length polymorphisms (AFLP) in four populations of the common vole Microtus arvalis for loci associated with local adaptation and high altitude. We investigated voles from two populations at high elevation (~2000 m a.s.l.) representing the upper limit of the altitudinal distribution of the species and two geographically close low-altitude populations (<600 m a.s.l.). Statistical analysis incorporated a new Bayesian F(ST) outlier approach specifically developed for AFLP markers, which considers the intensity of AFLP bands instead of mere presence/absence and allows to derive population-based estimates of allele frequencies and F(IS) values. Computer simulations showed that this approach increases the statistical power of the detection of AFLP markers under selection almost to the power of single nucleotide polymorphism (SNP) data without compromising specificity. Our enhanced genome scan resulted in 20 prime candidate markers for positive selection, which show mostly extremely high allele frequency differences between the low- and high-altitude populations. The comparison of global- and pairwise-enhanced genome scans demonstrated further that very strong selective signatures may also be associated with single populations suggesting the importance of local adaptation in alpine populations of common voles. 相似文献
42.
Tsai CH Singh P Chen CW Thomas J Weber J Mauch-Mani B Zimmerli L 《The Plant journal : for cell and molecular biology》2011,65(3):469-479
The priming agent β-aminobutyric acid (BABA) is known to enhance Arabidopsis resistance to the bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000 by potentiating salicylic acid (SA) defence signalling, notably PR1 expression. The molecular mechanisms underlying this phenomenon remain unknown. A genome-wide microarray analysis of BABA priming during Pst DC3000 infection revealed direct and primed up-regulation of genes that are responsive to SA, the SA analogue benzothiadiazole and pathogens. In addition, BABA was found to inhibit the Arabidopsis response to the bacterial effector coronatine (COR). COR is known to promote bacterial virulence by inducing the jasmonic acid (JA) response to antagonize SA signalling activation. BABA specifically repressed the JA response induced by COR without affecting other plant JA responses. This repression was largely SA-independent, suggesting that it is not caused by negative cross-talk between SA and JA signalling cascades. Treatment with relatively high concentrations of purified COR counteracted BABA inhibition. Under these conditions, BABA failed to protect Arabidopsis against Pst DC3000. BABA did not induce priming and resistance in plants inoculated with a COR-deficient strain of Pst DC3000 or in the COR-insensitive mutant coi1-16. In addition, BABA blocked the COR-dependent re-opening of stomata during Pst DC3000 infection. Our data suggest that BABA primes for enhanced resistance to Pst DC3000 by interfering with the bacterial suppression of Arabidopsis SA-dependent defences. This study also suggests the existence of a signalling node that distinguishes COR from other JA responses. 相似文献
43.
F.9 embryonal carcinoma cell calcitonin autocrine system: correlation between immunoreactive calcitonin secretion and calcitonin receptor number 总被引:2,自引:0,他引:2
Mouse teratocarcinoma cells in culture offer an in vitro system to study the initial steps of embryogenesis. It has been suggested that, at such early stages, cell functions are regulated by an autocrine process in which embryonic cells produce factors that in turn act on themselves. F.9 cells possess specific membrane receptors for calcitonin (CT) (120 fmol/mg of protein, Ka, = 3.5 X 10(8) M-1). These cells produce CT detected by heterologous radioimmunoassay in serum-free culture-conditioned medium (75 pg/10(7) cells/12 h). When F.9 cells are incubated in serum-free medium, CT binding and secretion concomitantly drop by 50% within the first 2 h, then increase progressively to an upper plateau after the sixth hour. Preincubation with 10(-6) M CT leads to disappearance of CT receptors and CT secretion in the culture medium up to 6 h. Avoiding accumulation of CT in the medium by a continuous flow rate for 6 h leads to a progressive decrease of CT receptors. In addition, retinoic acid treatment of cells induces a parallel progressive decrease of CT receptor number and of total CT synthesis. These results suggest a reciprocal regulation of CT receptors and CT secretion, or a close relationship between their regulations. 相似文献
44.
Mechkarska M Ojo OO Meetani MA Coquet L Jouenne T Abdel-Wahab YH Flatt PR King JD Conlon JM 《Peptides》2011,32(2):203-208
Using a combination of reversed-phase HPLC and electrospray mass spectrometry, peptidomic analysis of norepinephrine-stimulated skin secretions of the American bullfrog Lithobates catesbeianus Shaw, 1802 led to the identification and characterization of five newly described peptides (ranatuerin-1CBb, ranatuerin-2CBc, and -CBd, palustrin-2CBa, and temporin-CBf) together with seven peptides previously isolated on the basis of their antimicrobial activity (ranatuerin-1CBa, ranatuerin-2CBa, brevinin-1CBa, and -1CBb, temporin-CBa, -CBb, and -CBd). The abilities of the most abundant of the purified peptides to stimulate the release of insulin from the rat BRIN-BD11 clonal β cell line were evaluated. Ranatuerin-2CBd (GFLDIIKNLGKTFAGHMLDKIRCTIGTCPPSP) was the most potent peptide producing a significant stimulation of insulin release (119% of basal rate, P < 0.01) from BRIN-BD11 cells at a concentration of 30 nM, with a maximum response (236% of basal rate, P < 0.001) at a concentration of 3 μM. Ranatuerin-2CBd did not stimulate release of the cytosolic enzyme, lactate dehydrogenase at concentrations up to 3 μM, indicating that the integrity of the plasma membrane had been preserved. Brevinin-1CBb (FLPFIARLAAKVFPSIICSVTKKC) produced the maximum stimulation of insulin release (285% of basal rate, P < 0.001 at 3 μM) but the peptide was cytotoxic at this concentration. 相似文献
45.
Scott Bennett Thomas Wernberg Thibaut de Bettignies Gary A. Kendrick Robert J. Anderson John J. Bolton Kirsten L. Rodgers Nick T. Shears Jean‐Charles Leclerc Laurent Lévêque Dominique Davoult Hartvig C. Christie 《Ecology letters》2015,18(7):677-686
Species interactions are integral drivers of community structure and can change from competitive to facilitative with increasing environmental stress. In subtidal marine ecosystems, however, interactions along physical stress gradients have seldom been tested. We observed seaweed canopy interactions across depth and latitudinal gradients to test whether light and temperature stress structured interaction patterns. We also quantified interspecific and intraspecific interactions among nine subtidal canopy seaweed species across three continents to examine the general nature of interactions in subtidal systems under low consumer pressure. We reveal that positive and neutral interactions are widespread throughout global seaweed communities and the nature of interactions can change from competitive to facilitative with increasing light stress in shallow marine systems. These findings provide support for the stress gradient hypothesis within subtidal seaweed communities and highlight the importance of canopy interactions for the maintenance of subtidal marine habitats experiencing environmental stress. 相似文献
46.
Jean-François Fournier Yushma Bhurruth-Alcor Branislav Musicki Jérome Aubert Michèle Aurelly Claire Bouix-Peter Karinne Bouquet Laurent Chantalat Marion Delorme Bénédicte Drean Gwenaelle Duvert Nicolas Fleury-Bregeot Blanche Gauthier Karine Grisendi Craig S. Harris Laurent F. Hennequin Tatiana Isabet Florence Joly Loïc Tomas 《Bioorganic & medicinal chemistry letters》2018,28(17):2985-2992
A series of squaramide-based hydroxamic acids were designed, synthesized and evaluated against human HDAC enzyme. Squaramides were found to be potent in the Hut78 cell line, but initially suffered from low solubility. Leads with improved solubility and metabolic profiles were shown to be class I, IIB and IV selective. 相似文献
47.
Laurent Blairon Mengi L. Maza Ingrid Wybo Denis Piérard Anne Dediste Olivier Vandenberg 《Anaerobe》2010,16(4):355-361
The Vitek 2 Anaerobe and Corynebacterium Identification Card (ANC) was recently evaluated in a multicentre study. In the present work, this system was compared with the BBL Crystal Anaerobe and RapID ANA II panels. These kits were tested using 196 strains of anaerobes that had been previously identified by gas–liquid chromatography. Identification to the species or to the genus level was 75.0%, 81.1% and 70.9% for Crystal, RapID and Vitek, respectively. Vitek ANC failed to provide any identification in 20.4% of the strains, but it had fewer misidentifications than RapID. The confidence factors provided on the results report of each kit were not always correlated with a lower risk of major errors, with the exception of Vitek 2 in which a confidence factor higher than 0.86 excluded the risk of misidentification in more than 87% of isolates. The lower rate of identification by the Vitek and Crystal panels is mostly due the lower ability of these systems to identify the Clostridia. Overall, the three panels are comparable but need improvement to a better accuracy. 相似文献
48.
Silvina Dayer Laurent J Lamarque Rgis Burlett Giovanni Bortolami Sylvain Delzon Jos C Herrera Herv Cochard Gregory A Gambetta 《Plant physiology》2022,190(3):1673
Climate change is challenging the resilience of grapevine (Vitis), one of the most important crops worldwide. Adapting viticulture to a hotter and drier future will require a multifaceted approach including the breeding of more drought-tolerant genotypes. In this study, we focused on plant hydraulics as a multi-trait system that allows the plant to maintain hydraulic integrity and gas exchange rates longer under drought. We quantified a broad range of drought-related traits within and across Vitis species, created in silico libraries of trait combinations, and then identified drought tolerant trait syndromes. By modeling the maintenance of hydraulic integrity of current cultivars and the drought tolerant trait syndromes, we identified elite ideotypes that increased the amount of time they could experience drought without leaf hydraulic failure. Generally, elites exhibited a trait syndrome with lower stomatal conductance, earlier stomatal closure, and a larger hydraulic safety margin. We demonstrated that, when compared with current cultivars, elite ideotypes have the potential to decrease the risk of hydraulic failure across wine regions under future climate scenarios. This study reveals the syndrome of traits that can be leveraged to protect grapevine from experiencing hydraulic failure under drought and increase drought tolerance.This article quantifies the diversity of hydraulic traits across grapevine genotypes and reveals the trait combinations that can help increase grapevine drought tolerance. 相似文献
49.
Cédric Rébé Rodolphe Filomenko Magalie Raveneau Angélique Chevriaux Minako Ishibashi Laurent Lagrost Jean Louis Junien Philippe Gambert David Masson 《PloS one》2012,7(11)
Background
Liver X receptor (LXR) α and LXR β (NR1H3 and NR1H2) are oxysterol-activated nuclear receptors involved in the control of major metabolic pathways such as cholesterol homeostasis, lipogenesis, inflammation and innate immunity. Synthetic LXR agonists are currently under development and could find applications in various fields such as cardiovascular diseases, cancer, diabetes and neurodegenerative diseases. The clinical development of LXR agonists requires the identification of biological markers for pharmacodynamic studies. In this context, monocytes represent an attractive target to monitor LXR activation. They are easily accessible cells present in peripheral blood; they express LXR α and β and respond to LXR agonist stimulation in vitro. The aim of our study was to identify cell surface markers of LXR agonists on monocytes. For this, we focused on clusters of differentiation (CD) markers because they are well characterized and accessible cell surface molecules allowing easy immuno-phenotyping.Methodology/Principal Findings
By using microarray analysis of monocytes treated or not with an LXR agonist in vitro, we selected three CD, i.e. CD82, CD226, CD244 for further analysis by real time PCR and flow cytometry. The three CD were up-regulated by LXR agonist treatment in vitro in a time- and dose- dependent manner and this induction was LXR specific as assessed by a SiRNA or LXR antagonist strategy. By using flow cytometry, we could demonstrate that the expression of these molecules at the cell surface of monocytes was significantly increased after LXR agonist treatment.Conclusions/Significance
We have identified three new cell surface markers that could be useful to monitor LXR activation. Future studies will be required to confirm the biological and diagnostic significance of the markers. 相似文献50.