全文获取类型
收费全文 | 1902篇 |
免费 | 180篇 |
出版年
2023年 | 13篇 |
2022年 | 31篇 |
2021年 | 41篇 |
2020年 | 20篇 |
2019年 | 27篇 |
2018年 | 31篇 |
2017年 | 39篇 |
2016年 | 56篇 |
2015年 | 76篇 |
2014年 | 96篇 |
2013年 | 114篇 |
2012年 | 150篇 |
2011年 | 147篇 |
2010年 | 87篇 |
2009年 | 82篇 |
2008年 | 109篇 |
2007年 | 99篇 |
2006年 | 103篇 |
2005年 | 107篇 |
2004年 | 113篇 |
2003年 | 82篇 |
2002年 | 86篇 |
2001年 | 23篇 |
2000年 | 16篇 |
1999年 | 22篇 |
1998年 | 27篇 |
1997年 | 14篇 |
1996年 | 21篇 |
1995年 | 27篇 |
1994年 | 19篇 |
1993年 | 11篇 |
1992年 | 10篇 |
1991年 | 7篇 |
1990年 | 10篇 |
1989年 | 10篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 7篇 |
1985年 | 15篇 |
1984年 | 12篇 |
1983年 | 7篇 |
1982年 | 9篇 |
1981年 | 7篇 |
1980年 | 9篇 |
1977年 | 6篇 |
1975年 | 7篇 |
1972年 | 7篇 |
1971年 | 5篇 |
1969年 | 5篇 |
1967年 | 5篇 |
排序方式: 共有2082条查询结果,搜索用时 31 毫秒
971.
Key questions remain about the regulation and limits of cardiac function in fish challenged with elevated temperature, and to what extent sex differences influence cardiac performance. In this study, we investigated the in vivo relationship between heart rate (fH), stroke volume (SV), and cardiac output (Q) in quiescent, sexually immature rainbow trout (Oncorhynchus mykiss Walbaum) when challenged with: (1) an acute increase in water temperature from 14 to 24 °C at 2 °C h−1 and (2) a 50% reduction in fH at 24 °C, achieved through the incremental administration of zatebradine hydrochloride (total dose 2 mg kg body mass−1). There were no statistically significant (P<0.05) sex differences in cardiovascular function as temperature was raised to 24 °C. In males (N=10) and females (N=9), fH increased in a linear fashion with water temperature (from ∼60 beats min−1 at 14 °C to ∼125 beats min−1 at 24 °C; Q10=2.1), SV was largely unchanged, and systemic blood pressure (PDA) increased only slightly (by approx. 0.5 kPa) because the potential effect of increased Q on PDA was mostly offset by a 35% decrease in systemic vascular resistance (Rsys). At 24 °C, zatebradine treatment halved fH in both sexes, and yet Q was maintained at pre-treatment levels due to a doubling of SV. Overall, these results: (1) indicate that the in vivo cardiovascular response of quiescent, immature, male and female trout to elevated temperature is similar and (2) challenge the current dogma about how temperature affects cardiac function in fishes. Specifically, unlike previous in vitro or in situ studies, our data demonstrate that fish are capable of maintaining or even increasing SV at high temperatures. This suggests that aspects of cardiac control favor an increase in fH as temperatures rise, or that increases in cardiac output to meet the fish’s metabolic demands at high temperatures are met solely through an increase in fH because tachycardia is a requisite (unavoidable) physiological response. 相似文献
972.
Williams NL Morris JL Rush C Govan BL Ketheesan N 《FEMS immunology and medical microbiology》2011,61(2):218-227
Diabetes mellitus is a documented risk factor for melioidosis, a tropical infection caused by Burkholderia pseudomallei. The increased susceptibility of diabetic individuals to infections with other pathogens has been associated with immune dysregulation. However, the impact of diabetes on the functional responses of dendritic cells (DC) and macrophages during B. pseudomallei infection has not been investigated. This study compared the responses of macrophages and DC towards B. pseudomallei using bone marrow-derived DC (BMDC) and peritoneal elicited macrophages (PEM) isolated from streptozotocin-induced diabetic C57BL/6 mice exhibiting hyperglycaemia for 9 days (acute) or 70 days (chronic) and age-matched nondiabetic C57BL/6 mice. Following coincubation of BMDC and PEM with a highly virulent B. pseudomallei isolate, maturation, bacterial internalization plus intracellular survival and cytokine gene expression profiles were assessed. No significant differences in functional responses of BMDC or PEM isolated from acute diabetic and nondiabetic mice were observed. However, significant differences in BMDC and PEM function were observed when chronic diabetic and nondiabetic mice were compared. This study demonstrates that diabetic mice with extended periods of uncontrolled hyperglycaemia have impaired DC and macrophage function towards B. pseudomallei, which may contribute to the high susceptibility observed in clinical practice. 相似文献
973.
Laura E. Crotty Alexander Brenda J. Marsh Anjuli M. Timmer Ann E. Lin Kayvan Zainabadi Agnieszka Czopik Leonard Guarente Victor Nizet 《PloS one》2013,8(12)
The role of sirtuin-1 (SIRT1) in innate immunity, and in particular the influence of SIRT1 on antimicrobial defense against infection, has yet to be reported but is important to define since SIRT1 inhibitors are being investigated as therapeutic agents in the treatment of cancer, Huntington’s disease, and autoimmune diseases. Given the therapeutic potential of SIRT1 suppression, we sought to characterize the role of SIRT1 in host defense. Utilizing both pharmacologic methods and a genetic knockout, we demonstrate that SIRT1 expression has little influence on macrophage and neutrophil antimicrobial functions. Myeloid SIRT1 expression does not change mortality in gram-negative toxin-induced shock or gram-positive bacteremia, suggesting that therapeutic suppression of SIRT1 may be done safely without suppression of myeloid cell-specific immune responses to severe bacterial infections. 相似文献
974.
Leonardo Campagna Peter J. Van Coeverden de Groot Brenda L. Saunders Stephen N. Atkinson Diana S. Weber Markus G. Dyck Peter T. Boag Stephen C. Lougheed 《Ecology and evolution》2013,3(9):3152-3165
As global warming accelerates the melting of Arctic sea ice, polar bears (Ursus maritimus) must adapt to a rapidly changing landscape. This process will necessarily alter the species distribution together with population dynamics and structure. Detailed knowledge of these changes is crucial to delineating conservation priorities. Here, we sampled 361 polar bears from across the center of the Canadian Arctic Archipelago spanning the Gulf of Boothia (GB) and M'Clintock Channel (MC). We use DNA microsatellites and mitochondrial control region sequences to quantify genetic differentiation, estimate gene flow, and infer population history. Two populations, roughly coincident with GB and MC, are significantly differentiated at both nuclear (FST = 0.01) and mitochondrial (ΦST = 0.47; FST = 0.29) loci, allowing Bayesian clustering analyses to assign individuals to either group. Our data imply that the causes of the mitochondrial and nuclear genetic patterns differ. Analysis of mtDNA reveals the matrilineal structure dates at least to the Holocene, and is common to individuals throughout the species’ range. These mtDNA differences probably reflect both genetic drift and historical colonization dynamics. In contrast, the differentiation inferred from microsatellites is only on the scale of hundreds of years, possibly reflecting contemporary impediments to gene flow. Taken together, our data suggest that gene flow is insufficient to homogenize the GB and MC populations and support the designation of GB and MC as separate polar bear conservation units. Our study also provide a striking example of how nuclear DNA and mtDNA capture different aspects of a species demographic history. 相似文献
975.
Daniella Krämer Frances A. Lane Emma T. Steenkamp Brenda D. Wingfield P. Markus Wilken 《Fungal biology》2021,125(6):427-434
Sexual reproduction is ubiquitous in nature, and nowhere is this more so than in the fungi. Heterothallic behaviour is observed when there is a strict requirement of contact between two individuals of opposite mating type for sexual reproduction to occur. In contrast, a homothallic species can complete the entire sexual cycle in isolation, although several genetic mechanisms underpin this self-fertility. These can be inferred by characterising the structure and gene-content of the mating-type locus, which contains genes that are involved in the regulation of sexual reproduction. In this study, the genetic basis of homothallism in Thielaviopsis cerberus was investigated, the only known self-fertile species within this genus. Using genome sequencing and conventional molecular techniques, two versions of the mating-type locus were identified in this species. This is typical of species that have a unidirectional mating-type switching reproductive strategy. The first version was a self-fertile locus that contained four known mating-type genes, while the second was a self-sterile version with a single mating-type gene. The conversion from a self-fertile to a self-sterile locus is likely mediated by a homologous recombination event at two direct repeats present in the self-fertile locus, resulting in the deletion of three mating-type genes and one of the repeats. Both locus versions were present in isolates that were self-fertile, while self-sterility was caused by the presence of only a switched locus. This study provides a clear example of the architectural fluidity in the mating-type loci that is common among even closely related fungal species. 相似文献
976.
Brenda K. Rone Alexandre N. Zerbini Erin A. Falcone Erin L. Keene Gregory S. Schorr 《The Journal of wildlife management》2024,88(3):e22543
Harbor porpoises (Phocoena phocoena) are the only cetaceans routinely sighted in Hood Canal, a narrow fjord that comprises the western edge of Puget Sound, Washington, USA. Harbor porpoises are sensitive to anthropogenic sounds, including noise from recreational and commercial vessel traffic, and the United States Navy, which conducts military training and testing within Hood Canal that can include underwater sound sources. This study was funded as part of the Navy monitoring program to assess potential impacts of naval activities on cetaceans. We conducted vessel-based line-transect surveys for harbor porpoises in Hood Canal in 2022–2023 to derive seasonal estimates of abundance and density. We carried out surveys over 37 days and surveyed the entire canal twice per season totaling 2,176 km of on-effort track line. We recorded 809 on-effort harbor porpoise groups and 1,385 individuals. Seasonal abundance estimates were lowest in winter (308 animals, 95% CI = 189–503) and gradually increased through spring and summer to a peak of 1,336 animals (95% CI = 826–2,160) in fall. Overall porpoise density was highest in central Hood Canal, an area that includes a designated United States Navy training range, though porpoise sightings were notably absent in a 21-km2 area adjacent to the naval submarine base within this otherwise high-density region. Though we collected only a single year of data, these results suggest that harbor porpoise abundance in Hood Canal increased significantly since it was last estimated (2013–2015). The notable seasonal fluctuation of harbor porpoise abundance suggests Hood Canal may host a larger percentage of the overall Washington Inland Waters stock during the fall season, raising important management considerations. 相似文献
977.
Brenda Cadiz-Rivera George Fromm Christina de Vries Jennifer Fields Kathleen E. McGrath Steven Fiering Michael Bulger 《PloS one》2014,9(5)
In mammals, the complex tissue- and developmental-specific expression of genes within the β-globin cluster is known to be subject to control by the gene promoters, by a locus control region (LCR) located upstream of the cluster, and by sequence elements located across the intergenic regions. Despite extensive investigation, however, the complement of sequences that is required for normal regulation of chromatin structure and gene expression within the cluster is not fully defined. To further elucidate regulation of the adult β-globin genes, we investigate the effects of two deletions engineered within the endogenous murine β-globin locus. First, we find that deletion of the β2-globin gene promoter, while eliminating β2-globin gene expression, results in no additional effects on chromatin structure or gene expression within the cluster. Notably, our observations are not consistent with competition among the β-globin genes for LCR activity. Second, we characterize a novel enhancer located 3′ of the β2-globin gene, but find that deletion of this sequence has no effect whatsoever on gene expression or chromatin structure. This observation highlights the difficulty in assigning function to enhancer sequences identified by the chromatin “landscape” or even by functional assays. 相似文献
978.
Jodi L. Humann Mark Wildung Derek Pouchnik Austin A. Bates Jennifer C. Drew Ursula N. Zipperer Eric W. Triplett Dorrie Main Brenda K. Schroeder 《Standards in genomic sciences》2014,9(3):726-734
The Enterobacter cloacae complex is genetically very diverse. The increasing number of complete genomic sequences of E. cloacae is helping to determine the exact relationship among members of the complex. E. cloacae P101 is an endophyte of switchgrass (Panicum virgatum) and is closely related to other E. cloacae strains isolated from plants. The P101 genome consists of a 5,369,929 bp chromosome. The chromosome has 5,164 protein-coding regions, 100 tRNA sequences, and 8 rRNA operons. 相似文献
979.
Species‐level view of population structure and gene flow for a critically endangered primate (Varecia variegata)
下载免费PDF全文
![点击此处可从《Ecology and evolution》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Andrea L. Baden Sheila M. Holmes Steig E. Johnson Shannon E. Engberg Edward E. Louis Jr Brenda J. Bradley 《Ecology and evolution》2014,4(13):2675-2692
Lemurs are among the world's most threatened mammals. The critically endangered black‐and‐white ruffed lemur (Varecia variegata), in particular, has recently experienced rapid population declines due to habitat loss, ecological sensitivities to habitat degradation, and extensive human hunting pressure. Despite this, a recent study indicates that ruffed lemurs retain among the highest levels of genetic diversity for primates. Identifying how this diversity is apportioned and whether gene flow is maintained among remnant populations will help to diagnose and target conservation priorities. We sampled 209 individuals from 19 sites throughout the remaining V. variegata range. We used 10 polymorphic microsatellite loci and ~550 bp of mtDNA sequence data to evaluate genetic structure and population dynamics, including dispersal patterns and recent population declines. Bayesian cluster analyses identified two distinct genetic clusters, which optimally partitioned data into populations occurring on either side of the Mangoro River. Localities north of the Mangoro were characterized by greater genetic diversity, greater gene flow (lower genetic differentiation) and higher mtDNA haplotype and nucleotide diversity than those in the south. Despite this, genetic differentiation across all sites was high, as indicated by high average FST (0.247) and ΦST (0.544), and followed a pattern of isolation‐by‐distance. We use these results to suggest future conservation strategies that include an effort to maintain genetic diversity in the north and restore connectivity in the south. We also note the discordance between patterns of genetic differentiation and current subspecies taxonomy, and encourage a re‐evaluation of conservation management units moving forward. 相似文献
980.
Michael C. Brothers Brett Geissler Grant S. Hisao Karla J. F. Satchell Brenda A. Wilson Chad M. Rienstra 《Biomolecular NMR assignments》2014,8(1):221-224
1H, 13C, and 15N chemical shift assignments are presented for the isolated four-helical bundle membrane localization domain (MLD) from Pasteurella multocida toxin (PMT) in its solution state. We have assigned 99 % of all backbone and side-chain carbon atoms, including 99 % of all backbone residues excluding proline amide nitrogens. Secondary chemical shift analysis using TALOS+ demonstrates four helices, which align with those observed within the MLD in the crystal structure of the C-terminus of PMT (PDB 2EBF) and confirm the use of the available crystal structures as templates for the isolated MLDs. 相似文献