全文获取类型
收费全文 | 1187篇 |
免费 | 137篇 |
出版年
2022年 | 10篇 |
2021年 | 9篇 |
2018年 | 8篇 |
2017年 | 11篇 |
2016年 | 24篇 |
2015年 | 28篇 |
2014年 | 34篇 |
2013年 | 54篇 |
2012年 | 60篇 |
2011年 | 49篇 |
2010年 | 37篇 |
2009年 | 36篇 |
2008年 | 46篇 |
2007年 | 39篇 |
2006年 | 51篇 |
2005年 | 58篇 |
2004年 | 40篇 |
2003年 | 50篇 |
2002年 | 50篇 |
2001年 | 45篇 |
2000年 | 44篇 |
1999年 | 40篇 |
1998年 | 14篇 |
1997年 | 8篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 18篇 |
1993年 | 12篇 |
1992年 | 26篇 |
1991年 | 24篇 |
1990年 | 20篇 |
1989年 | 32篇 |
1988年 | 45篇 |
1987年 | 21篇 |
1986年 | 20篇 |
1985年 | 22篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 10篇 |
1981年 | 14篇 |
1980年 | 9篇 |
1979年 | 11篇 |
1976年 | 9篇 |
1974年 | 16篇 |
1973年 | 12篇 |
1972年 | 11篇 |
1971年 | 10篇 |
1970年 | 7篇 |
1969年 | 9篇 |
1968年 | 7篇 |
排序方式: 共有1324条查询结果,搜索用时 359 毫秒
81.
Christopher M Grulke Kathleen Holm Michael-Rock Goldsmith Yu-Mei Tan 《Bioinformation》2013,9(13):707-709
As increasing amounts of biomonitoring survey data become available, a new discipline focused on converting such data into
estimates of chemical exposures has developed. Reverse dosimetry uses a pharmacokinetic model along with measured biomarker
concentrations to determine the plausible exposure concentrations-- a critical step to incorporate ground-truthing experimental
data into a distribution of probable exposures that reduces model uncertainty and variability. At the population level, probabilistic
reverse dosimetry can utilize a distribution of measured biomarker concentrations to identify the most likely exposure
concentrations (or intake doses) experienced by the study participants. PROcEED is software that provides access to probabilistic
reverse dosimetry approaches for estimating exposure distributions via a simple user interface.
Availability
PROcEED along with installation instructions is freely available for download from http://www.epa.gov/heasd/products/proceed/proceed.html 相似文献82.
Adam Ahanchédé José E. F. Alfaya L. W. Andersen Didier Azam Ma. Anita M. Bautista Anne‐Laure Besnard Gregorio Bigatti Anthony Bouétard Marie‐Agnès Coutellec Eben‐Ezer B. K. Ewédjè Reiko Fuseya Ricardo GarcÍa‐Jiménez M. Haratian Olivier J. Hardy L.‐E. Holm Casey W. Hoy Eriko Koshimizu V. Loeschcke Violeta López‐Márquez Carlos A. Machado Annie Machordom C. Marchi Andrew P. Michel Claire Micheneau Omprakash Mittapalli Takahiro Nagai Nobuaki Okamoto Ying Pan F. Panitz N. Safaie Takashi Sakamoto B. Sharifnabi En‐Wei Tian Hui Yu 《Molecular ecology resources》2013,13(1):158-159
This article documents the addition of 83 microsatellite marker loci and 96 pairs of single‐nucleotide polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Bembidion lampros, Inimicus japonicus, Lymnaea stagnalis, Panopea abbreviata, Pentadesma butyracea, Sycoscapter hirticola and Thanatephorus cucumeris (anamorph: Rhizoctonia solani). These loci were cross‐tested on the following species: Pentadesma grandifolia and Pentadesma reyndersii. This article also documents the addition of 96 sequencing primer pairs and 88 allele‐specific primers or probes for Plutella xylostella. 相似文献
83.
Karina D. Thielsen Jakob M. Moser Thomas Schmitt-John Morten S. Jensen Kimmo Jensen Mai Marie Holm 《PloS one》2013,8(12)
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease. It is a fatal degenerative disease, best recognized for its debilitating neuromuscular effects. ALS however also induces cognitive impairments in as many as 50% of affected individuals. Moreover, many ALS patients demonstrate cortical hyperexcitability, which has been shown to precede the onset of clinical symptoms. The wobbler mouse is a model of ALS, and like ALS patients the wobbler mouse displays cortical hyperexcitability. Here we investigated if the neocortical aberrations of the wobbler mouse also occur in the hippocampus. Consequently, we performed extracellular field excitatory postsynaptic potential recordings in the CA1 region of the hippocampus on acute brain slices from symptomatic (P45-P60) and presymptomatic (P17-P21) wobbler mice. Significant increased excitation of hippocampal synapses was revealed by leftward shifted input/output-curves in both symptomatic and presymptomatic wobbler mice, and substantiated by population spike occurrence analyses, demonstrating that the increased synaptic excitation precedes the onset of visible phenotypic symptoms in the mouse. Synaptic facilitation tested by paired-pulse facilitation and trains in wobbler and control mice showed no differences, suggesting the absence of presynaptic defects. Immunohistochemical staining revealed that symptomatic wobbler mice have a lower number of parvalbumin positive interneurons when compared to controls and presymptomatic mice. This study reveals that the wobbler mouse model of ALS exhibits hippocampal hyperexcitability. We suggest that the hyperexcitability could be caused by increased excitatory synaptic transmission and a concomitant reduced inhibition due to a decreased number of parvalbumin positive interneurons. Thus we substantiate that wobbler brain impairments are not confined to the motor cortex, but extend to the hippocampus. Importantly, we have revealed more details of the early pathophysiology in asymptomatic animals, and studies like the present may facilitate the development of novel treatment strategies for earlier intervention in ALS patients in the future. 相似文献
84.
85.
A comparative perspective on longevity: the effect of body size dominates over ecology in moths
下载免费PDF全文
![点击此处可从《Journal of evolutionary biology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
S. Holm R. B. Davis J. Javoiš E. Õunap A. Kaasik F. Molleman T. Tammaru 《Journal of evolutionary biology》2016,29(12):2422-2435
Both physiologically and ecologically based explanations have been proposed to account for among‐species differences in lifespan, but they remain poorly tested. Phylogenetically explicit comparative analyses are still scarce and those that exist are biased towards homoeothermic vertebrates. Insect studies can significantly contribute as lifespan can feasibly be measured in a high number of species, and the selective forces that have shaped it may differ largely between species and from those acting on larger animals. We recorded adult lifespan in 98 species of geometrid moths. Phylogenetic comparative analyses were applied to study variation in species‐specific values of lifespan and to reveal its ecological and life‐history correlates. Among‐species and between‐gender differences in lifespan were found to be notably limited; there was also no evidence of phylogenetic signal in this trait. Larger moth species were found to live longer, with this result supporting a physiological rather than ecological explanation of this relationship. Species‐specific lifespan values could not be explained by traits such as reproductive season and larval diet breadth, strengthening the evidence for the dominance of physiological determinants of longevity over ecological ones. 相似文献
86.
Anne-Marie Lundsgaard Jacob B. Holm Kim A. Sjøberg Kirstine N. Bojsen-Møller Lene S. Myrmel Even Fjære Benjamin A.H. Jensen Trine S. Nicolaisen Janne R. Hingst Sine L. Hansen Sophia Doll Philip E. Geyer Atul S. Deshmukh Jens J. Holst Lise Madsen Karsten Kristiansen Jørgen F.P. Wojtaszewski Erik A. Richter Bente Kiens 《Cell metabolism》2019,29(1):50-63.e4
87.
Kobayashi T Antar AA Boehme KW Danthi P Eby EA Guglielmi KM Holm GH Johnson EM Maginnis MS Naik S Skelton WB Wetzel JD Wilson GJ Chappell JD Dermody TS 《Cell host & microbe》2007,1(2):147-157
Mammalian orthoreoviruses (reoviruses) are highly tractable experimental models for studies of double-stranded (ds) RNA virus replication and pathogenesis. Reoviruses infect respiratory and intestinal epithelium and disseminate systemically in newborn animals. Until now, a strategy to rescue infectious virus from cloned cDNA has not been available for any member of the Reoviridae family of dsRNA viruses. We report the generation of viable reovirus following plasmid transfection of murine L929 (L) cells using a strategy free of helper virus and independent of selection. We used the reovirus reverse genetics system to introduce mutations into viral capsid proteins sigma1 and sigma3 and to rescue a virus that expresses a green fluorescent protein (GFP) transgene, thus demonstrating the tractability of this technology. The plasmid-based reverse genetics approach described here can be exploited for studies of reovirus replication and pathogenesis and used to develop reovirus as a vaccine vector. 相似文献
88.
Florentina Negoita Julia Blomdahl Sebastian Wasserstrom Martin E. Winberg Peter Osmark Sara Larsson Karin G. Stenkula Mattias Ekstedt Stergios Kechagias Cecilia Holm Helena A. Jones 《Journal of cellular biochemistry》2019,120(1):343-356
The mechanism of how patatin-like phospholipase domain-containing protein 3 (PNPLA3) variant M148 is associated with increased risk of development of hepatic steatosis is still debated. Here, we propose a novel role of PNPLA3 as a key player during autophagosome formation in the process of lipophagy. A human hepatocyte cell line, HepG2 cells, expressing recombinant I148 or 148M, was used to study lipophagy under energy deprived conditions, and lipid droplet morphology was investigated using florescence microscopy, image analysis and biochemical assays. Autophagic flux was studied using the golden-standard of LC3-II turnover in combination with the well characterized GFP-RFP-LC3 vector. To discriminate between, perturbed autophagic initiation and lysosome functionality, lysosomes were characterized by Lysotracker staining and LAMP1 protein levels as well as activity and activation of cathepsin B. For validation, human liver biopsies genotyped for I148 and 148M were analyzed for the presence of LC3-II and PNPLA3 on lipid droplets. We show that the M148-PNPLA3 variant is associated with lipid droplets that are resistant to starvation-mediated degradation. M148 expressing hepatocytes reveal decreased autophagic flux and reduced lipophagy. Both I148-PNPLA3 and M148-PNPLA3 colocalize and interact with LC3-II, but the M148-PNPLA3 variant has lower ability to bind LC3-II. Together, our data indicate that PNPLA3 might play an essential role in lipophagy in hepatocytes and furthermore that the M148-PNPLA3 variant appears to display a loss in this activity, leading to decreased lipophagy. 相似文献
89.
O B Tysnes V M Steen G M Aarbakke H Holmsen 《The International journal of biochemistry》1991,23(3):305-310
1. Gel-filtered human platelets prelabeled with [32P]Pi or [3H]glycerol were exposed to 0-0.3 U/ml of thrombin and analyzed for radioactivities and masses in the phosphoinositides, inositol trisphosphates (IP3), phosphatidic acid (PA) and diacylglycerol (DAG) at 15 and 180 sec of stimulation. 2. At thrombin concentrations below 0.1 U/ml, PA and IP3 accumulated in equimolar amounts. 3. The production and disappearance of the metabolites of the polyphosphoinositide cycle was balanced during 180 sec of stimulation with 0.03-0.1 U/ml of thrombin. 4. Under these conditions no increase in [3H]DAG or [3H]monoacylglycerol could be detected. 5. The data indicate that all DAG is converted to PA and support our conclusion that phosphatidylinositol 4,5-bisphosphate represents the major source for production of DAG upon stimulation of human platelets with low concentrations of thrombin. 相似文献
90.
Ploug M Østergaard S Gårdsvoll H Kovalski K Holst-Hansen C Holm A Ossowski L Danø K 《Biochemistry》2001,40(40):12157-12168
The high-affinity interaction between urokinase-type plasminogen activator (uPA) and its glycolipid-anchored receptor (uPAR) plays an important role in pericellular plasminogen activation. Since proteolytic degradation of the extracellular matrix has an established role in tumor invasion and metastasis, the uPA-uPAR interaction represents a potential target for therapeutic intervention. By affinity maturation using combinatorial chemistry we have now developed and characterized a 9-mer, linear peptide antagonist of the uPA-uPAR interaction demonstrating specific, high-affinity binding to human uPAR (K(d) approximately 0.4 nM). Studies by surface plasmon resonance reveal that the off-rate for this receptor-peptide complex is comparable to that measured for the natural protein ligand, uPA. The functional epitope on human uPAR for this antagonist has been delineated by site-directed mutagenesis, and its assignment to loop 3 of uPAR domain III (Met(246), His(249), His(251), and Phe(256)) corroborates data previously obtained by photoaffinity labeling and provides a molecular explanation for the extreme selectivity observed for the antagonist toward human compared to mouse, monkey, and hamster uPAR. When human HEp-3 cancer cells were inoculated in the presence of this peptide antagonist, a specific inhibition of cancer cell intravasation was observed in a chicken chorioallantoic membrane assay. These data imply that design of small organic molecules mimicking the binding determinants of this 9-mer peptide antagonist may have a potential application in combination therapy for certain types of cancer. 相似文献