全文获取类型
收费全文 | 108831篇 |
免费 | 1589篇 |
国内免费 | 814篇 |
出版年
2023年 | 48篇 |
2022年 | 147篇 |
2021年 | 272篇 |
2020年 | 124篇 |
2019年 | 220篇 |
2018年 | 11996篇 |
2017年 | 10827篇 |
2016年 | 7788篇 |
2015年 | 1200篇 |
2014年 | 1007篇 |
2013年 | 1171篇 |
2012年 | 5404篇 |
2011年 | 14015篇 |
2010年 | 12762篇 |
2009年 | 8872篇 |
2008年 | 10804篇 |
2007年 | 12407篇 |
2006年 | 1202篇 |
2005年 | 1450篇 |
2004年 | 1882篇 |
2003年 | 1955篇 |
2002年 | 1611篇 |
2001年 | 393篇 |
2000年 | 262篇 |
1999年 | 172篇 |
1998年 | 210篇 |
1997年 | 168篇 |
1996年 | 133篇 |
1995年 | 119篇 |
1994年 | 122篇 |
1993年 | 152篇 |
1992年 | 140篇 |
1991年 | 143篇 |
1990年 | 99篇 |
1989年 | 88篇 |
1988年 | 98篇 |
1987年 | 85篇 |
1986年 | 67篇 |
1985年 | 92篇 |
1984年 | 109篇 |
1983年 | 102篇 |
1982年 | 87篇 |
1981年 | 101篇 |
1980年 | 92篇 |
1979年 | 56篇 |
1978年 | 56篇 |
1977年 | 66篇 |
1976年 | 51篇 |
1972年 | 267篇 |
1971年 | 279篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
991.
Syeda Mehpara Farhat Aamra Mahboob Ghazala Iqbal Touqeer Ahmed 《Biological trace element research》2017,177(1):115-121
Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer’s disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl3 (250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication. 相似文献
992.
Fontán-Lozano A López-Lluch G Delgado-García JM Navas P Carrión AM 《Molecular neurobiology》2008,38(2):167-177
Aging is associated with the decline of cognitive properties. This situation is magnified when neurodegenerative processes
associated with aging appear in human patients. Neuronal synaptic plasticity events underlie cognitive properties in the central
nervous system. Caloric restriction (CR; either a decrease in food intake or an intermittent fasting diet) can extend life
span and increase disease resistance. Recent studies have shown that CR can have profound effects on brain function and vulnerability
to injury and disease. Moreover, CR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance
synaptic plasticity, which modulate pain sensation, enhance cognitive function, and may increase the ability of the brain
to resist aging. The beneficial effects of CR appear to be the result of a cellular stress response stimulating the production
of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic
factors, neurotransmitter receptors, protein chaperones, and mitochondrial biosynthesis regulators. In this review, we will
present and discuss the effect of CR in synaptic processes underlying analgesia and cognitive improvement in healthy, sick,
and aging animals. We will also discuss the possible role of mitochondrial biogenesis induced by CR in regulation of neuronal
synaptic plasticity. 相似文献
993.
Roh SW Kim KH Nam YD Chang HW Kim MS Yoon JH Oh HM Bae JW 《Journal of microbiology (Seoul, Korea)》2008,46(5):525-529
A novel bacterium B9T was isolated from tidal flat sediment. Its morphology, physiology, biochemical features, and 16S rRNA gene sequence were
characterized. Colonies of this strain are yellow and the cells are Gram-negative, rod-shaped, and do not require NaCl for
growth. The 16S rRNA gene sequence similarity indicated that strain B9T is associated with the genus Lysobacter (≤ 97.2%), Xanthomonas (≤ 96.8%), Pseudomonas (≤ 96.7%), and Luteimonas (≤ 96.0%). However, within the phylogenetic tree, this novel strain shares a branching point with the species Luteimonas composti CC-YY255T (96.0%). The DNA-DNA hybridization experiments showed a DNA-DNA homology of 23.0% between strain B9T and Luteimonas mephitis B1953/27.1T. The G+C content of genomic DNA of the type strain is 64.7 mol% (SD, 1.1). The predominant fatty acids are iso-C11:0, iso-C15:0, iso-C16:0, iso-C17:0, iso-C17:0
ω9c, and iso-C11:0 3-OH. Combined analysis of the 16S rRNA gene sequences, fatty acid profile, and results from physiological and biochemical
tests indicated that there is genotypic and phenotypic differentiation of the isolate from other Luteimonas species. For these reasons, strain B9T was proposed as a novel species, named Luteimonas aestuarii. The type strain of the new species is B9T (= KCTC 22048T, DSM 19680T). 相似文献
994.
Molecular identification and dynamics of microbial communities in reactor treating organic household waste 总被引:1,自引:0,他引:1
Juliana Cardinali-Rezende Renan B. Debarry Luis F. D. B. Colturato Eduardo V. Carneiro Edmar Chartone-Souza Andrea M. A. Nascimento 《Applied microbiology and biotechnology》2009,84(4):777-789
The prokaryotic diversity associated with organic household waste (OHW), leachate (start-up inoculum), and mesophilic anaerobic
digestion processes in the degradation of OHW for 44 and 90 days was investigated using a culture-independent approach. Bacterial
and archaeal 16S rRNA and mcrA gene clone libraries were constructed from community DNA preparations. Bacterial clones were affiliated with 13 phyla, of
which Firmicutes, Proteobacteria, and Bacteroidetes were represented in all libraries, whereas Actinobacteria, Thermotogae, Lentisphaerae, Acidobacteria, Chloroflexi, Cyanobacteria, Synergistetes, Spirochaetes, Deferribacteres, and Deinococcus-Thermus were exclusively identified in a single library. Within the Archaea domain, the Euryarchaeota phylum was the only one represented. Corresponding sequences were associated with the following orders of hydrogenotrophic
methanogens: Methanomicrobiales (Methanoculleus genus) and Methanobacteriales (Methanosphaera and Methanobacterium genera). One archaeal clone was not affiliated with any order and may represent a novel taxon. Diversity indices showed greater
diversity of Bacteria when compared to methanogenic Archaea. 相似文献
995.
Bert van Loo Jaap Kingma Gertjan Heyman Alex Wittenaar Jeffrey H. Lutje Spelberg Theo Sonke Dick B. Janssen 《Enzyme and microbial technology》2009,44(3):145-153
In epoxide hydrolase from Agrobacterium radiobacter (EchA), phenylalanine 108 flanks the nucleophilic aspartate and forms part of the substrate-binding pocket. The influence of mutations at this position on the activity and enantioselectivity of the enzyme was investigated. Screening for improved enantioselectivity towards para-nitrophenyl glycidyl ether (pNPGE) using spectrophotometric progress curve analysis yielded five different mutants with 3- to 7-fold improved enantioselectivity. The increase in enantioselectivity was in most cases the result of an enhanced catalytic efficiency toward the preferred enantiomer. Several mutations at position F108 resulted in a higher activity toward cis-disubstituted meso-epoxides, which were converted to a single product enantiomer. Mutant F108C converted cis-2,3-epoxybutane to (2R,3R)-2,3-butanediol of >99% ee with a 7-fold improved activity, and mutant F108A hydrolyzed cyclohexene oxide to (1R,2R)-1,2-cyclohexanediol of >99% ee with a more than 150-fold higher activity than wild-type enzyme. It is concluded that single amino acid substitutions in the active site of epoxide hydrolase can result in enzyme variants with catalytic properties that are suitable for preparative scale production of (S)-epoxides and chiral vicinal diols in high yield and with excellent ee. 相似文献
996.
Cd2+ provokes inositol trisphosphateproduction and releases stored Ca2+, apparently by binding to a zinc site in the external domain of an orphan receptor. One pM Cd2+ evokes an immediate spike in cytosolic free Ca2+, which is similar to that evoked by bradykinin. Platelet-derived growth factor (PDGF) also increases free Ca2+ in human dermalfibroblasts, but there is a distinct lag before free Ca2+ rises in response to PDGF. Genistein, which selectively inhibits tyrosine kinases, markedly inhibited Ca2+ mobilization evoked by PDGF. Calcium mobilization triggered by cadmium or bradykinin was relatively insensitive to genistein. The PDGF receptor is known to be a tyrosine kinase, whichphosphorylates and thereby activatesphospholipase C, whereas a G protein couples the bradykinin receptor to anotherphospholipase C isoform. These findings support the hypothesis that the orphan receptor triggered by cadmium is coupled to phospholipase C via a G protein.Abbreviations BSA
bovine serum albumin
- BK
bradykinin
- [Ca2+]i
cytosolic free calcium
- DME
Dulbecco's modified Eagle's medium
- FBS
fetal bovine serum
- HEPES
4-(2-hydroxyethyl)-1-piperazine-ethanesulfonic acid
- IC50
concentration that produces 50% inhibition
- PDGF
platelet-derived growth factor
- PSS
physiological salts solution
- SE
standard error of the mean 相似文献
997.
Analysis of trehalose-6-phosphate synthase (TPS) gene family suggests the formation of TPS complexes in rice 总被引:2,自引:0,他引:2
Trehalose-6-phosphate (T6P), an intermediate in the trehalose biosynthesis pathway, is emerging as an important regulator
of plant metabolism and development. T6P levels are potentially modulated by a group of trehalose-6-phosphate synthase (TPS)
and trehalose-6-phosphate phosphatase (TPP) homologues. In this study, we have isolated 11 TPS genes encoding proteins with both TPS and TPP domains, from rice. Functional complement assays performed in yeast tps1 and tps2 mutants, revealed that only OsTPS1 encodes an active TPS enzyme and no OsTPS protein possesses TPP activity. By using a yeast two-hybrid analysis, a complicated
interaction network occurred among OsTPS proteins, and the TPS domain might be essential for this interaction to occur. The
interaction between OsTPS1 and OsTPS8 in vivo was confirmed by bimolecular fluorescence complementation and coimmunoprecipitation
assays. Furthermore, our gel filtration assay showed that there may exist two forms of OsTPS1 (OsTPS1a and OsTPS1b) with different
elution profiles in rice. OsTPS1b was particularly cofractionated with OsTPS5 and OsTPS8 in the 360 kDa complex, while OsTPS1a
was predominantly incorporated into the complexes larger than 360 kDa. Collectively, these results suggest that OsTPS family members may form trehalose-6-phosphate synthase complexes and therefore potentially modify T6P levels to regulate
plant development. 相似文献
998.
Eduard Akhunov Charles Nicolet Jan Dvorak 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2009,119(3):507-517
Single nucleotide polymorphisms (SNPs) are indispensable in such applications as association mapping and construction of high-density
genetic maps. These applications usually require genotyping of thousands of SNPs in a large number of individuals. Although
a number of SNP genotyping assays are available, most of them are designed for SNP genotyping in diploid individuals. Here,
we demonstrate that the Illumina GoldenGate assay could be used for SNP genotyping of homozygous tetraploid and hexaploid
wheat lines. Genotyping reactions could be carried out directly on genomic DNA without the necessity of preliminary PCR amplification.
A total of 53 tetraploid and 38 hexaploid homozygous wheat lines were genotyped at 96 SNP loci. The genotyping error rate
estimated after removal of low-quality data was 0 and 1% for tetraploid and hexaploid wheat, respectively. Developed SNP genotyping
assays were shown to be useful for genotyping wheat cultivars. This study demonstrated that the GoldenGate assay is a very
efficient tool for high-throughput genotyping of polyploid wheat, opening new possibilities for the analysis of genetic variation
in wheat and dissection of genetic basis of complex traits using association mapping approach.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
999.
Miyamoto K Okunishi M Nukui E Tsuchiya T Kobayashi T Imada C Tsujibo H 《Archives of microbiology》2007,188(6):619-628
1000.
Pectinase was immobilized on a sodium alginate support using glutaraldehyde and retained 66% activity. The optimal pH for
activity shifted from 3.0 to 3.5 after immobilization; however, the optimum temperature remained unchanged at 40°C. The immobilized
enzyme also had a higher thermal stability and reusability than the free enzyme, and retained 80% of initial activity after
11 batch reactions. 相似文献