首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   811篇
  免费   85篇
  2022年   6篇
  2021年   10篇
  2020年   3篇
  2019年   8篇
  2018年   16篇
  2017年   19篇
  2016年   32篇
  2015年   38篇
  2014年   30篇
  2013年   39篇
  2012年   56篇
  2011年   54篇
  2010年   43篇
  2009年   26篇
  2008年   40篇
  2007年   41篇
  2006年   32篇
  2005年   44篇
  2004年   38篇
  2003年   43篇
  2002年   22篇
  2001年   17篇
  2000年   20篇
  1999年   18篇
  1998年   7篇
  1997年   9篇
  1996年   8篇
  1995年   7篇
  1994年   7篇
  1993年   8篇
  1992年   19篇
  1991年   16篇
  1990年   18篇
  1989年   12篇
  1988年   13篇
  1987年   10篇
  1986年   14篇
  1985年   11篇
  1984年   6篇
  1983年   9篇
  1982年   4篇
  1981年   4篇
  1980年   2篇
  1979年   2篇
  1978年   5篇
  1972年   1篇
  1965年   1篇
  1964年   1篇
  1956年   1篇
  1938年   1篇
排序方式: 共有896条查询结果,搜索用时 15 毫秒
71.
72.
The cuticle of the nematomorpha Gordius villoti is a proteinaceous extracellular structure that covers the body during the endoparasitic life in the hemocoelic cavity of insect hosts, and of the free-living adult animals. The ultrastructure of the cuticle has a complex spatial organization with several parallel layers of large diameter fibers, interposed thinner fibrous elements and honeycomb-shaped matrix surrounding the fibers. When adult isolated cuticles were partially solubilized by several compounds, the structure revealed a strong insolubility and the main fibers were always observable. HPLC and spectrophotometric assays carried out to investigate the presence of tyrosine cross-linking, indicated such a mechanism as a key-element in the hardening process of the cuticle. Such data strongly suggest that the Gordius cuticle contains dityrosine compounds, whose formation is probably mediated by endogenous peroxidase activity.  相似文献   
73.
The epithelial cells of the integument of body, arms and tentacles of Sepia officinalis present on their apical membrane a well-organised brush border and show the morphological and histochemical characteristics of a typical absorptive epithelium. The ability of the integument to absorb amino acids was investigated both in the arms incubated in vitro and in a purified preparation of brush border membrane vesicles (BBMV). Autoradiographic pictures of the integument after incubation of the arms in sea-water with or without sodium, showed that proline intake was Na+-dependent, whereas leucine intake appeared to be a largely cation-independent process. Time course experiments of labelled leucine, proline and lysine uptakes in BBMV evidenced that these amino acids are accumulated within the vesicles in the presence of an inwardly directed sodium gradient. The sodium-driven accumulation proves that cationic and neutral amino acids are taken up by the apical membrane of the epithelium of Sepia integument through a secondary active mechanism. For leucine, a 90% inhibition of the uptake was recorded in the presence of a large excess of the substrate. In agreement with the autoradiography results, an analysis of the cation specificity transport in BBMV showed that leucine uptake had a low cation specificity, whereas lysine and proline uptakes were Na+-dependent. An excess of lysine and proline, which share with alanine two different transport systems in the gill epithelium of marine bivalves, reduced eucine uptake. The possible role of the absorptive ability of the integument in a carnivorous mollusc is discussed.  相似文献   
74.
75.
The stabilizing role of the disaccharide trehalose on beta-lactoglobulin (BLG) against its chemical denaturation both at native and acidic pH has been explored by means of time-resolved fluorescence of the probe acrylodan covalently bound to the unique free cysteine of BLG. The changes in acrylodan fluorescence lifetime with guanidinium chloride concentration reveal BLG sigmoidal denaturation profiles which depend upon the amount of trehalose in solution. When adding trehalose the transition midpoint shifts towards higher denaturant concentration. This effect has been measured by fitting the data with a two-state model whose parameters indicate that an almost 60% increase in the denaturation free energy is induced independently of trehalose concentrations and pH values. Fluorescence anisotropy measurements performed in the same conditions reveal that the internal dynamics are largely affected by the sugar, which makes the acrylodan environment more rigid, and by the denaturant that acts in the opposite way. The overall rotational diffusion of BLG suggests that trehalose affects the hydrodynamic properties of the solution in the proximity of the protein; tentative mechanisms are discussed.  相似文献   
76.
In a previous study, we showed that the silencing of the heavy subunit (FHC) offerritin, the central iron storage molecule in the cell, is accompanied by a modification in global gene expression. In this work, we explored whether different FHC amounts might modulate miRNA expression levels in K562 cells and studied the impact of miRNAs in gene expression profile modifications. To this aim, we performed a miRNA-mRNA integrative analysis in K562 silenced for FHC (K562shFHC) comparing it with K562 transduced with scrambled RNA (K562shRNA). Four miRNAs, namely hsa-let-7g, hsa-let-7f, hsa-let-7i and hsa-miR-125b, were significantly up-regulated in silenced cells. The remarkable down-regulation of these miRNAs, following FHC expression rescue, supports a specific relation between FHC silencing and miRNA-modulation. The integration of target predictions with miRNA and gene expression profiles led to the identification of a regulatory network which includes the miRNAs up-regulated by FHC silencing, as well as91 down-regulated putative target genes. These genes were further classified in 9 networks; the highest scoring network, “Cell Death and Survival, Hematological System Development and Function, Hematopoiesis”, is composed by 18 focus molecules including RAF1 and ERK1/2. We confirmed that, following FHC silencing, ERK1/2 phosphorylation is severely impaired and that RAF1 mRNA is significantly down-regulated. Taken all together, our data indicate that, in our experimental model, FHC silencing may affect RAF1/pERK1/2 levels through the modulation of a specific set of miRNAs and add new insights in to the relationship among iron homeostasis and miRNAs.  相似文献   
77.

Background

Epidemiological studies have suggested a possible role of trace elements (TE) in the etiology of several neurological diseases including Multiple Sclerosis (MS). Hair analysis provides an easy tool to quantify TE in human subjects, including patients with neurodegenerative diseases.

Objective

To compare TE levels in scalp hair from patients with MS and healthy controls from the same geographic area (Sicily).

Methods

ICP-MS was used to determine the concentrations of 21 elements (Ag, Al, As, Ba, Cd, Co, Cr, Cu, Fe, Li, Mn, Mo, Ni, Pb, Rb, Sb, Se, Sr, U, V and Zn) in scalp hair of 48 patients with relapsing–remitting Multiple Sclerosis compared with 51 healthy controls.

Results

MS patients showed a significantly lower hair concentration of aluminum and rubidium (median values: Al = 3.76 μg/g vs. 4.49 μg/g and Rb = 0.007 μg/g vs. 0.01 μg/g;) and higher hair concentration of U (median values U: 0.014 μg/g vs. 0.007 μg/g) compared to healthy controls. The percentages of MS patients showing hair elemental concentrations greater than the 95th percentile of controls were 20% for Ni, 19% for Ba and U, and 15% for Ag, Mo and Se. Conversely, the percentages of MS patients showing hair elemental concentrations lower than the 5th percentile of healthy controls were 27% for Al, 25% for Rb, 22% for Ag, 19% for Fe, and 16% for Pb. No significant association was found between levels of each TE and age, disease duration or Expanded Disability Status Scale (EDSS) score. After stratification by gender, healthy subjects did not show any significant difference in trace element levels, while MS patients showed significant differences (p<0.01) for the concentrations of Ag, Cr, Fe, Ni and Sr. No significant differences were also found, at p<0.01, in relation to the use of cigarettes, consume of water, vegetables and place of living.

Conclusion

The different distributions of TE in hair of MS patients compared to controls provides an additional indirect evidence of metabolic imbalance of chemical elements in the pathogenesis of this disease. The increase in U and decrease in Al and Rb levels in MS compared to controls require further assessments as well as the observed different distributions of other elements.  相似文献   
78.
During an anthrax outbreak at the Pollino National Park (Basilicata, Italy) in 2004, diseased cattle were buried and from these anthrax-foci Bacillus anthracis endospores still diffuse to the surface resulting in local accumulations. Recent data suggest that B. anthracis multiplies in soil outside the animal-host body. This notion is supported by the frequent isolation of B. anthracis from soil lacking one or both virulence plasmids. Such strains represent an evolutionary dead end, as they are likely no longer able to successfully infect new hosts. This loss of virulence plasmids is explained most simply by postulating a soil-borne life cycle of the pathogen. To test this hypothesis we investigated possible microevolution at two natural anthrax foci from the 2004 outbreak. If valid, then genotypes of strains isolated from near the surface at these foci should be on a different evolutionary trajectory from those below residing in deeper-laying horizons close to the carcass. Thus, the genetic diversity of B. anthracis isolates was compared conducting Progressive Hierarchical Resolving Assays using Nucleic Acids (PHRANA) and next generation Whole Genome Sequencing (WGS). PHRANA was not discriminatory enough to resolve the fine genetic relationships between the isolates. Conversely, WGS of nine isolates from near-surface and nine from near-carcass revealed five isolate specific SNPs, four of which were found only in different near-surface isolates. In support of our hypothesis, one surface-isolate lacked plasmid pXO1 and also harbored one of the unique SNPs. Taken together, our results suggest a limited soil-borne life cycle of B. anthracis.  相似文献   
79.
Urban landscapes are commonly considered too mundane and corrupted to be biotically interesting. Recent insect surveys employing 29 Malaise traps throughout Los Angeles, California, however, have uncovered breeding populations of two unexpected species of one of the most studied and familiar groups of organisms, Drosophila “fruit” flies. Unlike most introduced species of drosophilids, which breed in fresh or decaying fruits, these are specialized flower-breeders. A common species in the survey was Drosophila (Drosophila) gentica Wheeler and Takada, previously collected only once, in El Salvador. It belongs to the flavopilosa species group, all species of which have been known until now from central Chile, Argentina and Uruguay, to Veracruz, Mexico and the Caribbean, breeding in flowers of Cestrum (“jessamine”) and Sessea (Solanaceae). The Los Angeles populations are probably breeding in a native and/or introduced Cestrum; in addition, populations in San Luis Obispo County were visiting ornamental Cestrum. Drosophila gentica occurs as far north as San Francisco, where it was found breeding in Cestrum aurantiacum. D. gentica is redescribed and figured in detail for diagnostic and identification purposes. Specimens from Jamaica previously identified as D. gentica are a distinct species but are not formally described in lieu of complete male specimens. Rare in the Malaise traps was Drosophila (Sophophora) flavohirta Malloch, a common species in Australia on the blossoms of native Myrtaceae, found on introduced Eucalyptus in South Africa and both Eucalyptus and Syzygium in Madagascar; adults feed on myrtaceous pollen and nectar, larvae breed in the flowers. It is also redescribed in detail, including its unusual egg. This is the first New World report of this species; DNA sequences confirm it is a morphologically highly aberrant member of the D. melanogaster species group. This study reveals how intensive field sampling can uncover remarkable biodiversity in even the most urbanized areas.  相似文献   
80.
Proteins containing bromodomains are capable of binding to acetylated histone tails and have a role in recognizing and deciphering acetylated chromatin. Plant BET proteins contain one bromodomain. Twelve BET-encoding genes have been identified in the Arabidopsis genome. Two of these genes have been functionally characterized, one shows a role in seed germination, the other is involved in the establishment of leaf shape. Recently, we characterized a third AtBET gene, named GTE4. We demonstrated that GTE4 is involved in the activation and maintenance of cell division in the meristems and by this controls cell numbers in differentiated organs. Moreover, the quiescent center (QC) identity is partially lost in the apex of the primary root of gte4 mutant, and there is a premature switch from mitosis to endocycling. Genes involved in the retinoblastoma (RB)-E2F pathway, which is important for coupling cell division and cell differentiation in plants and animals, were either up or downregulated in the gte4 mutant. In this report we also show that the defect in germination observed in gte4 mutant seeds is not rescued by the action of GA3. Further the root pole of the mutant embryo shows irregular cytokinesis in the procambial stem cells, and the QC of the lateral root shows a partial, but not transient, loss of QC identity. These additional results reinforce the importance of GTE4 in the control of cell proliferation.Key words: arabidopsis, BET bromodomain, cell cycle, E2F, germination  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号