全文获取类型
收费全文 | 5690篇 |
免费 | 390篇 |
国内免费 | 7篇 |
出版年
2023年 | 45篇 |
2022年 | 105篇 |
2021年 | 173篇 |
2020年 | 102篇 |
2019年 | 170篇 |
2018年 | 204篇 |
2017年 | 182篇 |
2016年 | 223篇 |
2015年 | 285篇 |
2014年 | 292篇 |
2013年 | 437篇 |
2012年 | 410篇 |
2011年 | 449篇 |
2010年 | 296篇 |
2009年 | 271篇 |
2008年 | 272篇 |
2007年 | 273篇 |
2006年 | 207篇 |
2005年 | 193篇 |
2004年 | 172篇 |
2003年 | 142篇 |
2002年 | 125篇 |
2001年 | 101篇 |
2000年 | 116篇 |
1999年 | 85篇 |
1998年 | 61篇 |
1997年 | 34篇 |
1996年 | 33篇 |
1995年 | 30篇 |
1994年 | 21篇 |
1993年 | 20篇 |
1992年 | 26篇 |
1991年 | 24篇 |
1990年 | 21篇 |
1989年 | 33篇 |
1988年 | 18篇 |
1987年 | 21篇 |
1986年 | 25篇 |
1985年 | 16篇 |
1984年 | 30篇 |
1983年 | 24篇 |
1982年 | 27篇 |
1981年 | 16篇 |
1980年 | 36篇 |
1979年 | 30篇 |
1978年 | 33篇 |
1977年 | 27篇 |
1976年 | 15篇 |
1974年 | 14篇 |
1973年 | 14篇 |
排序方式: 共有6087条查询结果,搜索用时 14 毫秒
961.
Yasmina Mirassou Diana García-Moreno Clara M. Santiveri Jorge Santoro Montserrat Elías-Arnanz S. Padmanabhan M. Angeles Jiménez 《Biomolecular NMR assignments》2009,3(1):9-12
CdnL, a 164-residue protein essential for Myxococcus xanthus viability, is a member of a large family of bacterial proteins of unknown structure and function. Here, we report the 1H, 13C and 15N backbone and side chain assignments for the stable C-terminal domain of CdnL identified by limited proteolysis. 相似文献
962.
Background
The low and variable prevalence of Methanobrevibacter smithii and Methanosphaera stadtmanae DNA in human stool contrasts with the paramount role of these methanogenic Archaea in digestion processes. We hypothesized that this contrast is a consequence of the inefficiencies of current protocols for archaeon DNA extraction. We developed a new protocol for the extraction and PCR-based detection of M. smithii and M. stadtmanae DNA in human stool.Methodology/Principal Findings
Stool specimens collected from 700 individuals were filtered, mechanically lysed twice, and incubated overnight with proteinase K prior to DNA extraction using a commercial DNA extraction kit. Total DNA was used as a template for quantitative real-time PCR targeting M. smithii and M. stadtmanae 16S rRNA and rpoB genes. Amplification of 16S rRNA and rpoB yielded positive detection of M. smithii in 95.7% and M. stadtmanae in 29.4% of specimens. Sequencing of 16S rRNA gene PCR products from 30 randomly selected specimens (15 for M. smithii and 15 for M. stadtmanae) yielded a sequence similarity of 99–100% using the reference M. smithii ATCC 35061 and M. stadtmanae DSM 3091 sequences.Conclusions/Significance
In contrast to previous reports, these data indicate a high prevalence of the methanogens M. smithii and M. stadtmanae in the human gut, with the former being an almost ubiquitous inhabitant of the intestinal microbiome. 相似文献963.
Sami El Boustani Olivier Marre Sébastien Béhuret Pierre Baudot Pierre Yger Thierry Bal Alain Destexhe Yves Frégnac 《PLoS computational biology》2009,5(9)
Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of Vm activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the Vm reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the “effective” connectivity responsible for the dynamical signature of the population signals measured at different integration levels, from Vm to LFP, EEG and fMRI. 相似文献
964.
Maria Katsogiannou Charbel El Boustany Florian Gackiere Philippe Delcourt Anne Athias Pascal Mariot Etienne Dewailly Nathalie Jouy Christophe Lamaze Gabriel Bidaux Brigitte Mauroy Natalia Prevarskaya Christian Slomianny 《PloS one》2009,4(9)
Background
During androgen ablation prostate cancer cells'' growth and survival become independent of normal regulatory mechanisms. These androgen-independent cells acquire the remarkable ability to adapt to the surrounding microenvironment whose factors, such as neurotransmitters, influence their survival. Although findings are becoming evident about the expression of α1A-adrenoceptors in prostate cancer epithelial cells, their exact functional role in androgen-independent cells has yet to be established. Previous work has demonstrated that membrane lipid rafts associated with key signalling proteins mediate growth and survival signalling pathways in prostate cancer cells.Methodology/Principal Findings
In order to analyze the membrane topology of the α1A-adrenoceptor we explored its presence by a biochemical approach in purified detergent resistant membrane fractions of the androgen-independent prostate cancer cell line DU145. Electron microscopy observations demonstrated the colocalisation of the α1A-adrenoceptor with caveolin-1, the major protein component of caveolae. In addition, we showed that agonist stimulation of the α1A-adrenoceptor induced resistance to thapsigargin-induced apoptosis and that caveolin-1 was necessary for this process. Further, immunohistofluorescence revealed the relation between high levels of α1A-adrenoceptor and caveolin-1 expression with advanced stage prostate cancer. We also show by immunoblotting that the TG-induced apoptosis resistance described in DU145 cells is mediated by extracellular signal-regulated kinases (ERK).Conclusions/Significance
In conclusion, we propose that α1A-adrenoceptor stimulation in androgen-independent prostate cancer cells via caveolae constitutes one of the mechanisms contributing to their protection from TG-induced apoptosis. 相似文献965.
Claudia Hemp Klaus-Gerhard Heller Elżbieta Warchałowska-Śliwa Andreas Hemp 《Organisms Diversity & Evolution》2010,10(3):215-226
A new genus is proposed for a new East African Phaneropterinae species, Lunidia viridis, occurring on Mt. Kilimanjaro, Tanzania. Based on 33 records, notes on distribution and habitat are given, as well as acoustical
data provided. Climate and vegetation parameters obtained along several transects on Mt. Kilimanjaro were evaluated describing
the ecological niche of the new species. This interdisciplinary approach allows not only a profound characterisation of the
ecological demands of the new genus but also predictions of the potential distribution area, which is tested for the first
time for an African bush cricket species. Lunidia viridis n. gen. n. sp. occurs within humid and perhumid forests and Chagga home gardens, avoiding subhumid conditions on the mountain.
It is found from 1,330 m upwards on the southern slopes, whereas the same ecological conditions are expressed from 1,930 m
upwards on the drier northern slopes. Lunidia viridis has an unusually complex and variable song, which is described from field and laboratory recordings. The FISH technique for
characterizing chromosomes is applied for the first time for an African species; L. viridis exhibits a karyotype typical for most Tettigoniidae. 相似文献
966.
Fabrice Touzain Erick Denamur Claudine Médigue Valérie Barbe Meriem El Karoui Marie-Agnès Petit 《Genome biology》2010,11(4):R45
Background
Analysis of large scale diversity in bacterial genomes has mainly focused on elements such as pathogenicity islands, or more generally, genomic islands. These comprise numerous genes and confer important phenotypes, which are present or absent depending on strains. We report that despite this widely accepted notion, most diversity at the species level is composed of much smaller DNA segments, 20 to 500 bp in size, which we call microdiversity. 相似文献967.
Noomen Hmidet Nedra El Hadj Ali Nahed Zouari-Fakhfakh Anissa Haddar Moncef Nasri Alya Sellemi-Kamoun 《Journal of industrial microbiology & biotechnology》2010,37(9):983-990
This study is concerned with the co-production of alkaline proteases and thermostable α-amylase by some feather-degrading
Bacillus strains: B. mojavensis A21, B. licheniformis NH1, B. subtilis A26, B. amyloliquefaciens An6 and B. pumilus A1. All strains produced both enzymes, except B. pumilus A1, which did not exhibit amylolytic activity. The best enzyme co-production was obtained by the NH1 strain when chicken
feathers were used as nitrogen and carbon sources in the fermentation medium. The higher co-production of both enzymes by
B. licheniformis NH1 strain was achieved in the presence of 7.5 g/l chicken feathers and 1 g/l yeast extract. Strong catabolic repression
on protease and α-amylase production was observed with glucose. Addition of 0.5% glucose to the feather medium suppressed
enzyme production by B. licheniformis NH1. The growth of B. licheniformis NH1 using chicken feathers as nitrogen and carbon sources resulted in its complete degradation after 24 h of incubation at
37°C. However, maximum protease and amylase activities were attained after 30 h and 48 h, respectively. Proteolytic activity
profiles of NH1 enzymatic preparation grown on chicken feather or casein-based medium are different. As far as we know, this
is the first contribution towards the co-production of α-amylase and proteases using keratinous waste. Strain NH1 shows potential
use for biotechnological processes involving keratin hydrolysis and industrial α-amylase and proteases co-production. Thus,
the utilization of chicken feathers may result in a cost-effective process suitable for large-scale production. 相似文献
968.
Eléonore Durand Maud I Tenaillon Céline Ridel Denis Coubriche Philippe Jamin Sophie Jouanne Adrienne Ressayre Alain Charcosset Christine Dillmann 《BMC evolutionary biology》2010,10(1):2
Background
In order to investigate the rate and limits of the response to selection from highly inbred genetic material and evaluate the respective contribution of standing variation and new mutations, we conducted a divergent selection experiment from maize inbred lines in open-field conditions during 7 years. Two maize commercial seed lots considered as inbred lines, F252 and MBS847, constituted two biological replicates of the experiment. In each replicate, we derived an Early and a Late population by selecting and selfing the earliest and the latest individuals, respectively, to produce the next generation. 相似文献969.
El Abdellaoui H Varaprasad CV Barawkar D Chakravarty S Maderna A Tam R Chen H Allan M Wu JZ Appleby T Yan S Zhang W Lang S Yao N Hamatake R Hong Z 《Bioorganic & medicinal chemistry letters》2006,16(21):5561-5566
The development of potent, orally bioavailable, and selective series of 5-amino-3-hydroxy-N(1-hydroxypropane-2-yl)isothiazole-4-carboxamidine inhibitors of MEK1 and MEK-2 kinase is described. Optimization of the carboxamidine and the phenoxyaniline group led to the identification of 55 which gave good potency as in vitro MEK1 inhibitors, and good oral exposure in rat. 相似文献
970.
Synthesis and evaluation of phenoxy acetic acid derivatives as [corrected] anti-mycobacterial agents
Shaharyar M yar MS Siddiqui AA Ali MA 《Bioorganic & medicinal chemistry letters》2006,16(17):4571-4574
In present investigation, 2-(4-formyl-2-methoxyphenoxy) acetic acid on condensation with various ketones in methanolic KOH solution yielded the corresponding chalcones (1-3). These corresponding chalcones were reacted with appropriate acid hydrazide in glacial acetic acid led to the formation of phenoxy acetic acid derivatives. All newly synthesized compounds were evaluated for their anti-mycobacterial activities against Mycobacterium tuberculosis H(37)Rv. 相似文献