全文获取类型
收费全文 | 515篇 |
免费 | 30篇 |
国内免费 | 1篇 |
出版年
2023年 | 3篇 |
2022年 | 4篇 |
2021年 | 7篇 |
2019年 | 5篇 |
2018年 | 6篇 |
2017年 | 11篇 |
2016年 | 14篇 |
2015年 | 18篇 |
2014年 | 28篇 |
2013年 | 37篇 |
2012年 | 35篇 |
2011年 | 28篇 |
2010年 | 16篇 |
2009年 | 24篇 |
2008年 | 17篇 |
2007年 | 24篇 |
2006年 | 33篇 |
2005年 | 16篇 |
2004年 | 15篇 |
2003年 | 13篇 |
2002年 | 8篇 |
2001年 | 16篇 |
2000年 | 12篇 |
1999年 | 6篇 |
1998年 | 11篇 |
1997年 | 3篇 |
1996年 | 3篇 |
1995年 | 3篇 |
1994年 | 3篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 8篇 |
1989年 | 10篇 |
1988年 | 4篇 |
1987年 | 6篇 |
1986年 | 10篇 |
1985年 | 4篇 |
1984年 | 6篇 |
1982年 | 3篇 |
1981年 | 4篇 |
1979年 | 8篇 |
1978年 | 2篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1975年 | 7篇 |
1974年 | 4篇 |
1973年 | 4篇 |
1971年 | 4篇 |
1969年 | 3篇 |
1967年 | 2篇 |
排序方式: 共有546条查询结果,搜索用时 15 毫秒
101.
Juan Manuel Herrero-Medrano Hendrik-Jan Megens Martien AM Groenen Mirte Bosse Miguel Pérez-Enciso Richard PMA Crooijmans 《BMC genomics》2014,15(1)
Background
A major concern in conservation genetics is to maintain the genetic diversity of populations. Genetic variation in livestock species is threatened by the progressive marginalisation of local breeds in benefit of high-output pigs worldwide. We used high-density SNP and re-sequencing data to assess genetic diversity of local pig breeds from Europe. In addition, we re-sequenced pigs from commercial breeds to identify potential candidate mutations responsible for phenotypic divergence among these groups of breeds.Results
Our results point out some local breeds with low genetic diversity, whose genome shows a high proportion of regions of homozygosis (>50%) and that harbour a large number of potentially damaging mutations. We also observed a high correlation between genetic diversity estimates using high-density SNP data and Next Generation Sequencing data (r = 0.96 at individual level). The study of non-synonymous SNPs that were fixed in commercial breeds and also in any local breed, but with different allele, revealed 99 non-synonymous SNPs affecting 65 genes. Candidate mutations that may underlie differences in the adaptation to the environment were exemplified by the genes AZGP1 and TAS2R40. We also observed that highly productive breeds may have lost advantageous genotypes within genes involve in immune response – e.g. IL12RB2 and STAB1–, probably as a result of strong artificial in the intensive production systems in pig.Conclusions
The high correlation between genetic diversity computed with the 60K SNP and whole genome re-sequence data indicates that the Porcine 60K SNP Beadchip provides reliable estimates of genomic diversity in European pig populations despite the expected bias. Moreover, this analysis gave insights for strategies to the genetic characterization of local breeds. The comparison between re-sequenced local pigs and re-sequenced commercial pigs made it possible to report candidate mutations to be responsible for phenotypic divergence among those groups of breeds. This study highlights the importance of low input breeds as a valuable genetic reservoir for the pig production industry. However, the high levels of ROHs, inbreeding and potentially damaging mutations emphasize the importance of the genetic characterization of local breeds to preserve their genomic variability.Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-601) contains supplementary material, which is available to authorized users. 相似文献102.
103.
Ana C. Coan Brunno M. Campos Clarissa L. Yasuda Bruno Y. Kubota Felipe PG. Bergo Carlos AM. Guerreiro Fernando Cendes 《PloS one》2014,9(1)
Objective
Patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) have diffuse subtle gray matter (GM) atrophy detectable by MRI quantification analyses. However, it is not clear whether the etiology and seizure frequency are associated with this atrophy. We aimed to evaluate the occurrence of GM atrophy and the influence of seizure frequency in patients with TLE and either normal MRI (TLE-NL) or MRI signs of HS (TLE-HS).Methods
We evaluated a group of 172 consecutive patients with unilateral TLE-HS or TLE-NL as defined by hippocampal volumetry and signal quantification (122 TLE-HS and 50 TLE-NL) plus a group of 82 healthy individuals. Voxel-based morphometry was performed with VBM8/SPM8 in 3T MRIs. Patients with up to three complex partial seizures and no generalized tonic-clonic seizures in the previous year were considered to have infrequent seizures. Those who did not fulfill these criteria were considered to have frequent seizures.Results
Patients with TLE-HS had more pronounced GM atrophy, including the ipsilateral mesial temporal structures, temporal lobe, bilateral thalami and pre/post-central gyri. Patients with TLE-NL had more subtle GM atrophy, including the ipsilateral orbitofrontal cortex, bilateral thalami and pre/post-central gyri. Both TLE-HS and TLE-NL showed increased GM volume in the contralateral pons. TLE-HS patients with frequent seizures had more pronounced GM atrophy in extra-temporal regions than TLE-HS with infrequent seizures. Patients with TLE-NL and infrequent seizures had no detectable GM atrophy. In both TLE-HS and TLE-NL, the duration of epilepsy correlated with GM atrophy in extra-hippocampal regions.Conclusion
Although a diffuse network GM atrophy occurs in both TLE-HS and TLE-NL, this is strikingly more evident in TLE-HS and in patients with frequent seizures. These findings suggest that neocortical atrophy in TLE is related to the ongoing seizures and epilepsy duration, while thalamic atrophy is more probably related to the original epileptogenic process. 相似文献104.
Julio Massaharu Marubayashi Adi Kliot Valdir Atsushi Yuki Jorge Alberto Marques Rezende Renate Krause-Sakate Marcelo Agenor Pavan Murad Ghanim 《PloS one》2014,9(9)
Whiteflies (Hemiptera: Aleyrodidae) are sap-sucking insect pests, and some cause serious damage in agricultural crops by direct feeding and by transmitting plant viruses. Whiteflies maintain close associations with bacterial endosymbionts that can significantly influence their biology. All whitefly species harbor a primary endosymbiont, and a diverse array of secondary endosymbionts. In this study, we surveyed 34 whitefly populations collected from the states of Sao Paulo, Bahia, Minas Gerais and Parana in Brazil, for species identification and for infection with secondary endosymbionts. Sequencing the mitochondrial Cytochrome Oxidase I gene revealed the existence of five whitefly species: The sweetpotato whitefly Bemisia tabaci B biotype (recently termed Middle East-Asia Minor 1 or MEAM1), the greenhouse whitefly Trialeurodes vaporariorum, B. tabaci A biotype (recently termed New World 2 or NW2) collected only from Euphorbia, the Acacia whitefly Tetraleurodes acaciae and Bemisia tuberculata both were detected only on cassava. Sequencing rRNA genes showed that Hamiltonella and Rickettsia were highly prevalent in all MEAM1 populations, while Cardinium was close to fixation in only three populations. Surprisingly, some MEAM1 individuals and one NW2 population were infected with Fritschea. Arsenopnohus was the only endosymbiont detected in T. vaporariorum. In T. acaciae and B. tuberculata populations collected from cassava, Wolbachia was fixed in B. tuberculata and was highly prevalent in T. acaciae. Interestingly, while B. tuberculata was additionally infected with Arsenophonus, T. acaciae was infected with Cardinium and Fritschea. Fluorescence in situ hybridization analysis on representative individuals showed that Hamiltonella, Arsenopnohus and Fritschea were localized inside the bacteriome, Cardinium and Wolbachia exhibited dual localization patterns inside and outside the bacteriome, and Rickettsia showed strict localization outside the bacteriome. This study is the first survey of whitely populations collected in Brazil, and provides further insights into the complexity of infection with secondary endosymionts in whiteflies. 相似文献
105.
Salivary gland duct ligation is an alternative to gland excision for treating sialorrhea or reducing salivary gland size prior to tumor excision. Duct ligation also is used as an approach to study salivary gland aging, regeneration, radiotherapy, sialolithiasis and sialadenitis. Reports conflict about the contribution of each salivary cell population to gland size reduction after ductal ligation. Certain cell populations, especially acini, reportedly undergo atrophy, apoptosis and proliferation during reduction of gland size. Acini also have been reported to de-differentiate into ducts. These contradictory results have been attributed to different animal or salivary gland models, or to methods of ligation. We report here a bilateral double ligature technique for rabbit parotid glands with histologic observations at 1, 7, 14, 30, 60 days after ligation. A large battery of special stains and immunohistochemical procedures was employed to define the cell populations. Four stages with overlapping features were observed that led to progressive shutdown of gland activities: 1) marked atrophy of the acinar cells occurred by 14 days, 2) response to and removal of the secretory material trapped in the acinar and ductal lumens mainly between 30 and 60 days, 3) reduction in the number of parenchymal (mostly acinar) cells by apoptosis that occurred mainly between 14–30 days, and 4) maintenance of steady-state at 60 days with a low rate of fluid, protein, and glycoprotein secretion, which greatly decreased the number of leukocytes engaged in the removal of the luminal contents. The main post- ligation characteristics were dilation of ductal and acinar lumens, massive transient infiltration of mostly heterophils (rabbit polymorphonuclear leukocytes), acinar atrophy, and apoptosis of both acinar and ductal cells. Proliferation was uncommon except in the larger ducts. By 30 days, the distribution of myoepithelial cells had spread from exclusively investing the intercalated ducts pre-ligation to surrounding a majority of the residual duct-like structures, many of which clearly were atrophic acini. Thus, both atrophy and apoptosis made major contributions to the post-ligation reduction in gland size. Structures also occurred with both ductal and acinar markers that suggested acini differentiating into ducts. Overall, the reaction to duct ligation proceeded at a considerably slower pace in the rabbit parotid glands than has been reported for the salivary glands of the rat. 相似文献
106.
107.
Nitric oxide (NO) is a short lived diatomic free radical species synthesized by nitric oxide synthases (NOS). The physiological
roles of NO depend on its local concentrations as well as availability and the nature of downstream target molecules. At low
nanomolar concentrations, activation of soluble guanylyl cyclase (sGC) is the major event initiated by NO. The resulting elevation
in the intracellular cyclic GMP (cGMP) levels serves as signals for regulating diverse cellular and physiological processes.
The participation of NO and cGMP in diverse physiological processes is made possible through cell type specific spatio-temporal
regulation of NO and cGMP synthesis and signal diversity downstream of cGMP achieved through specific target selection. Thus
cyclic GMP directly regulates the activities of its downstream effectors such as Protein Kinase G (PKG), Cyclic Nucleotide
Gated channels (CNG) and Cyclic nucleotide phosphodiesterases, which in turn regulate the activities of a number of proteins
that are involved in regulating diverse cellular and physiological processes. Localization and activity of the NO-cGMP signaling
pathway components are regulated by G-protein coupled receptors, receptor and non receptor tyrosine kinases, phosphatases
and other signaling molecules. NO also serves as a powerful paracrine factor. At micromolar concentrations, NO reacts with
superoxide anion to form reactive peroxinitrite, thereby leading to the oxidation of important cellular proteins. Extensive
research efforts over the past two decades have shown that NO is an important modulator of axon outgrowth and guidance, synaptic
plasticity, neural precursor proliferation as well as neuronal survival. Excessive NO production as that evoked by inflammatory
signals has been identified as one of the major causative reasons for the pathogenesis of a number of neurodegenerative diseases
such as ALS, Alzheimers and Parkinson diseases. Regenerative therapies involving transplantation of embryonic stem cells (ES
cells) and ES cell derived lineage committed neural precursor cells have recently shown promising results in animal models
of Parkinson disease (PD). Recent studies from our laboratory have shown that a functional NO-cGMP signaling system is operative
early during the differentiation of embryonic stem cells. The cell type specific, spatio-temporally regulated NO-cGMP signaling
pathways are well suited for inductive signals to use them for important cell fate decision making and lineage commitment
processes. We believe that manipulating the NO-cGMP signaling system will be an important tool for large scale generation
of lineage committed precursor cells to be used for regenerative therapies.
Special issue dedicated to John P. Blass. 相似文献
108.
Jossi Hillel Martien AM Groenen Michèle Tixier-Boichard Abraham B Korol Lior David Valery M Kirzhner Terry Burke Asili Barre-Dirie Richard PMA Crooijmans Kari Elo Marcus W Feldman Paul J Freidlin Asko M?ki-Tanila Marian Oortwijn Pippa Thomson Alain Vignal Klaus Wimmers Steffen Weigend 《遗传、选种与进化》2003,35(6):533-557
In a project on the biodiversity of chickens funded by the European Commission (EC), eight laboratories collaborated to assess the genetic variation within and between 52 populations from a wide range of chicken types. Twenty-two di-nucleotide microsatellite markers were used to genotype DNA pools of 50 birds from each population. The polymorphism measures for the average, the least polymorphic population (inbred C line) and the most polymorphic population (Gallus gallus spadiceus) were, respectively, as follows: number of alleles per locus, per population: 3.5, 1.3 and 5.2; average gene diversity across markers: 0.47, 0.05 and 0.64; and proportion of polymorphic markers: 0.91, 0.25 and 1.0. These were in good agreement with the breeding history of the populations. For instance, unselected populations were found to be more polymorphic than selected breeds such as layers. Thus DNA pools are effective in the preliminary assessment of genetic variation of populations and markers. Mean genetic distance indicates the extent to which a given population shares its genetic diversity with that of the whole tested gene pool and is a useful criterion for conservation of diversity. The distribution of population-specific (private) alleles and the amount of genetic variation shared among populations supports the hypothesis that the red jungle fowl is the main progenitor of the domesticated chicken. 相似文献
109.
通过考察阿托伐他汀(atorvastatin, ATO) 对自发性高血压大鼠(spontaneously hypertensive rats, SHR) 肾脏炎性损害的影响, 探讨了 ATO 对高血压肾脏并发症的防治作用。将4周龄SHR分为高血压模型组和ATO治疗组(8mg/kg),以同周龄的Wistar-Kyoto大鼠为正常对照。灌胃给药8周后, 采用酶联免疫法(enzyme linked immunosorbent assay)测定血浆和肾组织血管紧张素Ⅱ(angiotensin, AngⅡ)含量;测定诱导性一氧化氮合酶(inducible nitric oxide synthase, iNOS)及细胞间粘附分子-1(intercellular adhesion molecule-1, ICAM-1) 的蛋白表达和亚硝酸阴离子(nitrite, NO2-)含量,以评价肾脏炎症状态; 以苏木素伊红(hematoxylin and eosin)和过碘酸六胺银染色(periodic acid-silver metheramine) 染色示SHR肾小球和肾间质形态学病变,并以尿蛋白含量为指标衡量肾脏功能。结果显示... 相似文献
110.
The particulate form of guanylyl cyclase from bovine rod outer segments has been solubilized and purified to near homogeneity by a combination of liquid chromatography and native gel electrophoresis. The procedure enriches enzyme activity 6700-fold from rod outer segment extracts to a final specific activity of 17.5 mumol/min per mg (when assayed with Mn-GTP as substrate). Purified preparations of guanylyl cyclase contain a single glycoprotein with an apparent molecular mass of 60,000 Da and a native isoelectric point of 7.6. Although crude or partially purified enzyme activity is modulated by sub-micromolar concentrations of Ca2+, the fully purified enzyme is insensitive to this cation. However, the purified enzyme remains sensitive to nitrovasodilators, being stimulated over 10-fold by sodium nitroprusside. These data suggest that retinal rods contain a unique isoform of guanylyl cyclase. 相似文献