全文获取类型
收费全文 | 1195篇 |
免费 | 82篇 |
专业分类
1277篇 |
出版年
2023年 | 2篇 |
2022年 | 7篇 |
2021年 | 19篇 |
2020年 | 10篇 |
2019年 | 12篇 |
2018年 | 14篇 |
2017年 | 21篇 |
2016年 | 36篇 |
2015年 | 60篇 |
2014年 | 70篇 |
2013年 | 78篇 |
2012年 | 112篇 |
2011年 | 111篇 |
2010年 | 69篇 |
2009年 | 60篇 |
2008年 | 89篇 |
2007年 | 73篇 |
2006年 | 51篇 |
2005年 | 77篇 |
2004年 | 71篇 |
2003年 | 49篇 |
2002年 | 50篇 |
2001年 | 22篇 |
2000年 | 10篇 |
1999年 | 12篇 |
1998年 | 12篇 |
1997年 | 9篇 |
1996年 | 4篇 |
1995年 | 5篇 |
1994年 | 8篇 |
1993年 | 6篇 |
1992年 | 7篇 |
1991年 | 6篇 |
1990年 | 6篇 |
1989年 | 2篇 |
1987年 | 3篇 |
1979年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1974年 | 1篇 |
1973年 | 5篇 |
1972年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1940年 | 1篇 |
排序方式: 共有1277条查询结果,搜索用时 15 毫秒
41.
Birkenfeld AL Lee HY Guebre-Egziabher F Alves TC Jurczak MJ Jornayvaz FR Zhang D Hsiao JJ Martin-Montalvo A Fischer-Rosinsky A Spranger J Pfeiffer AF Jordan J Fromm MF König J Lieske S Carmean CM Frederick DW Weismann D Knauf F Irusta PM De Cabo R Helfand SL Samuel VT Shulman GI 《Cell metabolism》2011,14(2):184-195
Reduced expression of the Indy (I'm Not Dead, Yet) gene in D.?melanogaster and its homolog in C.?elegans prolongs life span and in D.?melanogaster augments mitochondrial biogenesis in a manner akin to caloric restriction. However, the cellular mechanism by which Indy does this is unknown. Here, we report on the knockout mouse model of the mammalian Indy (mIndy) homolog, SLC13A5. Deletion of mIndy in mice (mINDY(-/-) mice) reduces hepatocellular ATP/ADP ratio, activates hepatic AMPK, induces PGC-1α, inhibits ACC-2, and reduces SREBP-1c levels. This signaling network promotes hepatic mitochondrial biogenesis, lipid oxidation, and energy expenditure and attenuates hepatic de novo lipogenesis. Together, these traits protect mINDY(-/-) mice from the adiposity and insulin resistance that evolve with high-fat feeding and aging. Our studies demonstrate a profound effect of mIndy on mammalian energy metabolism and suggest that mINDY might be a therapeutic target for the treatment of obesity and type 2 diabetes. 相似文献
42.
Background
Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man''s deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate) sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded.Methods
In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF) from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets.Results
In the MOF group serum total cholesterol and LDL decreased significantly (P≤0.05) by 5% (n = 11) and 7% (n = 9), respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05) in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P≤0.05).Conclusion
Our integrative multi-biomarker approach unveiled the pleiotropic vascular health benefit of an 8 weeks supplementation with 200 mg/d MOF in humans.Trial Registration
ClinicalTrials.gov NCT00742287相似文献43.
Zinger L Amaral-Zettler LA Fuhrman JA Horner-Devine MC Huse SM Welch DB Martiny JB Sogin M Boetius A Ramette A 《PloS one》2011,6(9):e24570
Background
Marine microbial communities have been essential contributors to global biomass, nutrient cycling, and biodiversity since the early history of Earth, but so far their community distribution patterns remain unknown in most marine ecosystems.Methodology/Principal Findings
The synthesis of 9.6 million bacterial V6-rRNA amplicons for 509 samples that span the global ocean''s surface to the deep-sea floor shows that pelagic and benthic communities greatly differ, at all taxonomic levels, and share <10% bacterial types defined at 3% sequence similarity level. Surface and deep water, coastal and open ocean, and anoxic and oxic ecosystems host distinct communities that reflect productivity, land influences and other environmental constraints such as oxygen availability. The high variability of bacterial community composition specific to vent and coastal ecosystems reflects the heterogeneity and dynamic nature of these habitats. Both pelagic and benthic bacterial community distributions correlate with surface water productivity, reflecting the coupling between both realms by particle export. Also, differences in physical mixing may play a fundamental role in the distribution patterns of marine bacteria, as benthic communities showed a higher dissimilarity with increasing distance than pelagic communities.Conclusions/Significance
This first synthesis of global bacterial distribution across different ecosystems of the World''s oceans shows remarkable horizontal and vertical large-scale patterns in bacterial communities. This opens interesting perspectives for the definition of biogeographical biomes for bacteria of ocean waters and the seabed. 相似文献44.
Giese B Glowinski F Paprotka K Dittmann S Steiner T Sinha B Fraunholz MJ 《Cellular microbiology》2011,13(2):316-329
Staphylococcus aureus is able to invade non-professional phagocytes by interaction of staphylococcal adhesins with extracellular proteins of mammalian cells and eventually resides in acidified phago-endosomes. Some staphylococcal strains have been shown to subsequently escape from this compartment. A functional agr quorum-sensing system is needed for phagosomal escape. However, the nature of this agr dependency as well as the toxins involved in disruption of the phagosomal membrane are unknown. Using a novel technique to detect vesicular escape of S. aureus, we identified staphylococcal virulence factors involved in phagosomal escape. Here we show that a synergistic activity of the cytolytic peptide, staphylococcal δ-toxin and the sphingomyelinase β-toxin enable the phagosomal escape of staphylococci in human epithelial as well as in endothelial cells. The agr dependency of this process can be directly explained by the location of the structural gene for δ-toxin within the agr effector RNAIII. 相似文献
45.
A subset of chemosensory genes differs between two populations of a specialized leaf beetle after host plant shift 下载免费PDF全文
Ding Wang Stefan Pentzold Maritta Kunert Marco Groth Wolfgang Brandt Jacques M. Pasteels Wilhelm Boland Antje Burse 《Ecology and evolution》2018,8(16):8055-8075
Due to its fundamental role in shaping host selection behavior, we have analyzed the chemosensory repertoire of Chrysomela lapponica. This specialized leaf beetle evolved distinct populations which shifted from the ancestral host plant, willow (Salix sp., Salicaceae), to birch (Betula rotundifolia, Betulaceae). We identified 114 chemosensory candidate genes in adult C. lapponica: 41 olfactory receptors (ORs), eight gustatory receptors, 17 ionotropic receptors, four sensory neuron membrane proteins, 32 odorant binding proteins (OBPs), and 12 chemosensory proteins (CSP) by RNA‐seq. Differential expression analyses in the antennae revealed significant upregulation of one minus‐C OBP (ClapOBP27) and one CSP (ClapCSP12) in the willow feeders. In contrast, one OR (ClapOR17), four minus‐C OBPs (ClapOBP02, 07, 13, 20), and one plus‐C OBP (ClapOBP32) were significantly upregulated in birch feeders. The differential expression pattern in the legs was more complex. To narrow down putative ligands acting as cues for host discrimination, the relative abundance and diversity of volatiles of the two host plant species were analyzed. In addition to salicylaldehyde (willow‐specific), both plant species differed mainly in their emission rate of terpenoids such as (E,E)‐α‐farnesene (high in willow) or 4,8‐dimethylnona‐1,3,7‐triene (high in birch). Qualitatively, the volatiles were similar between willow and birch leaves constituting an “olfactory bridge” for the beetles. Subsequent structural modeling of the three most differentially expressed OBPs and docking studies using 22 host volatiles indicated that ligands bind with varying affinity. We suggest that the evolution of particularly minus‐C OBPs and ORs in C. lapponica facilitated its host plant shift via chemosensation of the phytochemicals from birch as novel host plant. 相似文献
46.
47.
Jens Amendt Angela Zissler Lena Lutz Ildikò Szelecz Antje Habermann Stefan Pittner 《当今生物学》2020,50(1):58-64
Mulitdisciplinarity in forensics Estimating the time of death is an important task in forensic science. After 1–2 days, however, it is drastically complicated due to autolysis and decay of the body. Here, a combination of established and new methods from different disciplines can help. Morphological changes of the corpse are dependent on the post mortem interval (PMI) and can be classified using scoring systems: The age determination and analysis of species diversity of necrophagous insects developing on the corpse allows the colonisation time determined to the day, the degradation of proteins of skeletal muscles follows a characteristic, time-dependent degradation pattern, soil organisms underneath a decomposing body can be negatively affected by corpse fluids or benefit from the associated input of nutrients such as proteins, lipids and carbohydrates. The combined, interdisciplinary evaluation of all these parameters offers completely new possibilities for the determination of the PMI, even days, weeks and months after death. 相似文献
48.
Jana A. Eccard Antje Herde Andrea C. Schuster Thilo Liesenjohann Tatjana Knopp Gerald Heckel Melanie Dammhahn 《Ecology and evolution》2022,12(2)
Individuals of a population may vary along a pace‐of‐life syndrome from highly fecund, short‐lived, bold, dispersive “fast” types at one end of the spectrum to less fecund, long‐lived, shy, plastic “slow” types at the other end. Risk‐taking behavior might mediate the underlying life history trade‐off, but empirical evidence supporting this hypothesis is still ambiguous. Using experimentally created populations of common voles (Microtus arvalis)—a species with distinct seasonal life history trajectories—we aimed to test whether individual differences in boldness behavior covary with risk taking, space use, and fitness. We quantified risk taking, space use (via automated tracking), survival, and reproductive success (via genetic parentage analysis) in 8 to 14 experimental, mixed‐sex populations of 113 common voles of known boldness type in large grassland enclosures over a significant part of their adult life span and two reproductive events. Populations were assorted to contain extreme boldness types (bold or shy) of both sexes. Bolder individuals took more risks than shyer ones, which did not affect survival. Bolder males but not females produced more offspring than shy conspecifics. Daily home range and core area sizes, based on 95% and 50% Kernel density estimates (20 ± 10 per individual, n = 54 individuals), were highly repeatable over time. Individual space use unfolded differently for sex‐boldness type combinations over the course of the experiment. While day ranges decreased for shy females, they increased for bold females and all males. Space use trajectories may, hence, indicate differences in coping styles when confronted with a novel social and physical environment. Thus, interindividual differences in boldness predict risk taking under near‐natural conditions and have consequences for fitness in males, which have a higher reproductive potential than females. Given extreme inter‐ and intra‐annual fluctuations in population density in the study species and its short life span, density‐dependent fluctuating selection operating differently on the sexes might maintain (co)variation in boldness, risk taking, and pace‐of‐life. 相似文献
49.
50.
Agnes Csanadi Claudia Kayser Marcel Donauer Vera Gumpp Konrad Aumann Justyna Rawluk Antje Prasse Axel zur Hausen Sebastian Wiesemann Martin Werner Gian Kayser 《PloS one》2015,10(5)