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   2459篇
  免费   232篇
  国内免费   3篇
  2024年   6篇
  2023年   32篇
  2022年   50篇
  2021年   122篇
  2020年   80篇
  2019年   99篇
  2018年   96篇
  2017年   68篇
  2016年   119篇
  2015年   159篇
  2014年   167篇
  2013年   193篇
  2012年   211篇
  2011年   184篇
  2010年   122篇
  2009年   109篇
  2008年   132篇
  2007年   119篇
  2006年   104篇
  2005年   113篇
  2004年   78篇
  2003年   52篇
  2002年   53篇
  2001年   23篇
  2000年   7篇
  1999年   12篇
  1998年   13篇
  1997年   7篇
  1996年   6篇
  1995年   5篇
  1994年   6篇
  1993年   6篇
  1992年   9篇
  1991年   7篇
  1990年   7篇
  1989年   9篇
  1988年   12篇
  1987年   5篇
  1986年   7篇
  1985年   4篇
  1982年   3篇
  1980年   5篇
  1978年   3篇
  1971年   5篇
  1968年   4篇
  1963年   4篇
  1950年   3篇
  1938年   2篇
  1933年   2篇
  1919年   2篇
排序方式: 共有2694条查询结果,搜索用时 753 毫秒
51.
Gobies (Gobiidae sensu Gill & Mooi, 2012 Gill, A. and Mooi, R. 2012. Thalasseleotrididae, new family of marine gobioid fishes from New Zealand and temperate Australia, with a revised definition of its sister taxon, the Gobiidae (Teleostei: Acanthomorpha). Zootaxa, 3266: 4152.  [Google Scholar]) are one of the most diverse families of vertebrates, and comprise over 1700 species of marine, brackish and freshwater fishes. Phylogenetic studies based on morphological characters and mtDNA have suggested that goby diversity is asymmetrically split between a speciose clade of predominantly marine species, and a less rich, but ecologically diverse, clade comprising predominantly freshwater and brackish species. This study is the first to explore this deep divide in gobies and their relationships at the family level using phylogenetic data from nuclear genes (RAG1, rhodopsin). Our results confirm the split within the Gobiidae, and agree with prior molecular studies on the inclusion of the following taxa within the two goby clades: (i) the more diverse of the two clades of gobies (the ‘Gobiidae’ sensu stricto of Thacker 2009 Thacker, C. E. 2009. Phylogeny of Gobioidei and placement within Acanthomorpha, with a new classification and investigation of diversification and character evolution. Copeia, 1: 93104. doi:10.1643/CI-08-004[Crossref], [Web of Science ®] [Google Scholar]) comprises the gobiines, microdesmines, ptereleotrines and kraemeriines; (ii) the less diverse of the two gobiid clades (‘Gobionellidae’ sensu Thacker 2009 Thacker, C. E. 2009. Phylogeny of Gobioidei and placement within Acanthomorpha, with a new classification and investigation of diversification and character evolution. Copeia, 1: 93104. doi:10.1643/CI-08-004[Crossref], [Web of Science ®] [Google Scholar]) includes the gobionellines, oxudercines, amblyopines, sicydiines, as well as the European sand gobies. Some relationships within the two major gobiid clades remain unclear. Specifically, there remains confusion regarding the monophyly and interrelationships between the northern Pacific gobionellines, the Mugilogobius group gobionellines, and the European sand gobies. Additionally, within Thacker's (2009 Thacker, C. E. 2009. Phylogeny of Gobioidei and placement within Acanthomorpha, with a new classification and investigation of diversification and character evolution. Copeia, 1: 93104. doi:10.1643/CI-08-004[Crossref], [Web of Science ®] [Google Scholar]) Gobiidae sensu stricto, there are several well-supported groups (e.g. the wormfishes and dartfishes, the Coral Gobies, the Gobiosomatini), yet relationships among these groups are still poorly resolved despite the use of data from two conserved nuclear genes. Future phylogenetic analyses of gobies will benefit greatly from taxon sampling that includes groups that have been historically under-represented in molecular studies (e.g. European sand gobies, northern Pacific gobionellines, African species), as well as deeper genetic sampling including large numbers of independent loci from throughout the genome (i.e. a phylogenomic approach).  相似文献   
52.
Even though cardiovascular disease is the leading cause of death for men and women, the vast majority of animal studies use male animals. Because female reproductive hormones have been associated with cardioprotective states, many investigators avoid using female animals because these hormones are cyclical and may introduce experimental variability. In addition, no studies have investigated the specific effects of the estrous cycle on cardiac ischemic injury. This study was conducted to determine whether the estrous cycle stage influences the susceptibility to ischemic injury in rat hearts. Estrous cycle stage was determined by using vaginal smear cytology, after which hearts underwent either in vivo (surgical) or ex vivo (isolated) ischemia–reperfusion injury. For in vivo studies, the left anterior coronary artery was ligated for 25 min of ischemia and subsequently released for 120 min of reperfusion. Infarct sizes were 42% ± 6%; 49% ± 4%; 40% ± 9%; 47% ± 9% of the zone-at-risk for rats in proestrus, estrus, metestrus, and diestrus, respectively. For ex vivo studies, isolated, perfused hearts underwent global ischemia and reperfusion for 25 and 120 min, respectively. Similar to our in vivo studies, the ex vivo rat model showed no significant differences in susceptibility to infarction or extent of cardiac arrhythmia according to estrous stage. To our knowledge, these studies provide the first direct evidence that the stage of estrous cycle does not significantly alter cardiac ischemia–reperfusion injury in rats.Abbreviations: VF, ventricular fibrillation; VT, ventricular tachycardiaCardiovascular disease remains the leading cause of morbidity and mortality throughout the industrialized world, with ischemic heart disease being a major manifestation of cardiovascular disease. Many investigators use animal models to advance our understanding of the etiology and mechanisms involved. Although ischemic heart disease is the leading cause of death for both men and women, the overwhelming majority of studies use male animals. Perhaps the most common reason for this practice is that physiologic fluctuations in female reproductive hormones such as estrogen may be a confounding variable, given the influence of female reproductive hormones on various organ systems.25 Despite the assertion that cyclical variations in female reproductive hormones may confound experimental studies, few data are available that support estrous-cycle–dependent variations in susceptibility to ischemic heart injury.Epidemiologic studies suggest that, compared with men, women have lower cardiac mortality prior to undergoing menopause.40 Consistent with human studies, experimental models in several species commonly show that the degree of cardiac injury in young female animals is lower than that in male counterparts.7,9,21,22,42 Exogenous administration of estrogen has a clear effect in reducing injury,14,15 but whether endogenous cyclical variations in female reproductive hormones affect cardiac injury is not known.Rats and mice are commonly used species to examine cardiac ischemia–reperfusion injury. Unlike humans, rodents do not undergo menstruation, during which the uterine endometrium sloughs off and is expelled through the vagina, but rather the uterine lining of rodents is reabsorbed during an estrous cycle.24 The rat estrous cycle is typically 4 to 5 d in length and is defined by 4 separate stages: proestrus, estrus, metestrus, and diestrus. Proestrus is characterized by increasing levels of estrogen. At the end of proestrus, ovulation (signaled by luteinizing hormone) occurs and marks the beginning of the estrus cycle. During metestrus and diestrus, the uterine lining regenerates, and the cycle starts again.24,33 These stages induce changes in the composition of the epithelium of the vagina and the presence of inflammatory cells, which can easily be detected by using vaginal cytology.18,35We conducted the current study to determine whether estrous cycle stage influences the susceptibility to ischemia–reperfusion injury in the rat heart. Because the stage of the estrous cycle may influence cardiac injury either directly (via a direct effect of circulating hormones), or indirectly (by inducing changes that are intrinsic to the heart), we used both in vivo and ex vivo models of injury.  相似文献   
53.
54.

Background

Severe asthma is associated with T helper (TH) 2 and 17 cell activation, airway neutrophilia and phosphoinositide-3-kinase (PI3K) activation. Asthma exacerbations are commonly caused by rhinovirus (RV) and also associated with PI3K-driven inflammation. Anthraquinone derivatives have been shown to reduce PI3K-mediated AKT phosphorylation in-vitro.

Objective

To determine the anti-inflammatory potential of anthraquinones in-vivo.

Methods

BALB/c mice were sensitized and challenged with crude house dust mite extract to induce allergic airways disease and treated with mitoxantrone and a novel non-cytotoxic anthraquinone derivative. Allergic mice were also infected with RV1B to induce an exacerbation.

Results

Anthraquinone treatment reduced AKT phosphorylation, hypoxia-inducible factor-1α and vascular endothelial growth factor expression, and ameliorated allergen- and RV-induced airways hyprereactivity, neutrophilic and eosinophilic inflammation, cytokine/chemokine expression, mucus hypersecretion, and expression of TH2 proteins in the airways. Anthraquinones also boosted type 1 interferon responses and limited RV replication in the lung.

Conclusion

Non-cytotoxic anthraquinone derivatives may be of therapeutic benefit for the treatment of severe and RV-induced asthma by blocking pro-inflammatory pathways regulated by PI3K/AKT.  相似文献   
55.

Background

In order to promote infection, the blood-borne parasite Trypanosoma brucei releases factors that upregulate arginase expression and activity in myeloid cells.

Methodology/Principal findings

By screening a cDNA library of T. brucei with an antibody neutralizing the arginase-inducing activity of parasite released factors, we identified a Kinesin Heavy Chain isoform, termed TbKHC1, as responsible for this effect. Following interaction with mouse myeloid cells, natural or recombinant TbKHC1 triggered SIGN-R1 receptor-dependent induction of IL-10 production, resulting in arginase-1 activation concomitant with reduction of nitric oxide (NO) synthase activity. This TbKHC1 activity was IL-4Rα-independent and did not mirror M2 activation of myeloid cells. As compared to wild-type T. brucei, infection by TbKHC1 KO parasites was characterized by strongly reduced parasitaemia and prolonged host survival time. By treating infected mice with ornithine or with NO synthase inhibitor, we observed that during the first wave of parasitaemia the parasite growth-promoting effect of TbKHC1-mediated arginase activation resulted more from increased polyamine production than from reduction of NO synthesis. In late stage infection, TbKHC1-mediated reduction of NO synthesis appeared to contribute to liver damage linked to shortening of host survival time.

Conclusion

A kinesin heavy chain released by T. brucei induces IL-10 and arginase-1 through SIGN-R1 signaling in myeloid cells, which promotes early trypanosome growth and favors parasite settlement in the host. Moreover, in the late stage of infection, the inhibition of NO synthesis by TbKHC1 contributes to liver pathogenicity.  相似文献   
56.
Halomonas species are recognized for producing exopolysaccharides (EPS) exhibiting amphiphilic properties that allow these macromolecules to interface with hydrophobic substrates, such as hydrocarbons. There remains a paucity of knowledge, however, on the potential of Halomonas EPS to influence the biodegradation of hydrocarbons. In this study, the well-characterized amphiphilic EPS produced by Halomonas species strain TG39 was shown to effectively increase the solubilization of aromatic hydrocarbons and enhance their biodegradation by an indigenous microbial community from oil-contaminated surface waters collected during the active phase of the Deepwater Horizon oil spill. Three Halomonas strains were isolated from the Deepwater Horizon site, all of which produced EPS with excellent emulsifying qualities and shared high (97-100%) 16S rRNA sequence identity with strain TG39 and other EPS-producing Halomonas strains. Analysis of pyrosequence data from surface water samples collected during the spill revealed several distinct Halomonas phylotypes, of which some shared a high sequence identity (≥97%) to strain TG39 and the Gulf spill isolates. Other bacterial groups comprising members with well-characterized EPS-producing qualities, such as Alteromonas , Colwellia and Pseudoalteromonas , were also found enriched in surface waters, suggesting that the total pool of EPS in the Gulf during the spill may have been supplemented by these organisms. Roller bottle incubations with one of the Halomonas isolates from the Deepwater Horizon spill site demonstrated its ability to effectively produce oil aggregates and emulsify the oil. The enrichment of EPS-producing bacteria during the spill coupled with their capacity to produce amphiphilic EPS is likely to have contributed to the ultimate removal of the oil and to the formation of oil aggregates, which were a dominant feature observed in contaminated surface waters.  相似文献   
57.
58.
The class Eustigmatophyceae includes mostly coccoid, freshwater algae, although some genera are common in terrestrial habitats and two are primarily marine. The formal classification of the class, developed decades ago, does not fit the diversity and phylogeny of the group as presently known and is in urgent need of revision. This study concerns a clade informally known as the Pseudellipsoidion group of the order Eustigmatales, which was initially known to comprise seven strains with oval to ellipsoidal cells, some bearing a stipe. We examined those strains as well as 10 new ones and obtained 18S rDNA and rbcL gene sequences. The results from phylogenetic analyses of the sequence data were integrated with morphological data of vegetative and motile cells. Monophyly of the Pseudellipsoidion group is supported in both 18S rDNA and rbcL trees. The group is formalized as the new family Neomonodaceae comprising, in addition to Pseudellipsoidion, three newly erected genera. By establishing Neomonodus gen. nov. (with type species Neomonodus ovalis comb. nov.), we finally resolve the intricate taxonomic history of a species originally described as Monodus ovalis and later moved to the genera Characiopsis and Pseudocharaciopsis. Characiopsiella gen. nov. (with the type species Characiopsiella minima comb. nov.) and Munda gen. nov. (with the type species Munda aquilonaris) are established to accommodate additional representatives of the polyphyletic genus Characiopsis. A morphological feature common to all examined Neomonodaceae is the absence of a pyrenoid in the chloroplasts, which discriminates them from other morphologically similar yet unrelated eustigmatophytes (including other Characiopsis-like species).  相似文献   
59.
Coral Reefs - Cumulative anthropogenic pressures have triggered a global decline in the health of marine ecosystems, and coral reefs, in particular, are in crisis. With climate and...  相似文献   
60.
A previously undescribed skin abnormality, referred to as “linear skin markings” (LSM), has been identified in free-ranging common bottlenose dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida (IRL). The lesions were identified during photo-identification surveys conducted from 2002 and 2015. LSM presented as distinct, parallel lines running dorso-ventrally on the torso and varied in length and width. The goals of this study were to determine (1) prevalence of the condition in IRL dolphins, (2) age and sex distribution of affected animals, (3) spatial and temporal distribution patterns, (4) duration of the condition, and (5) development of hypotheses regarding the etiology of the condition. Among 1,357 individual dolphins identified during the study period, 96 (7.0%) showed evidence of LSM. Nearly all (98.8%) cases with an established home range occurred in the northern and central regions of the IRL. The majority of cases of known sex were female (85%), of which 100% had given birth to one or more calves. The mean age of animals with LSM when first observed was 7.3 with a range of 1–20 years. The maximum observed duration of LSM was 15 years. Once observed, the condition persisted indefinitely. The etiology of LSM has not been established.  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