全文获取类型
收费全文 | 5109篇 |
免费 | 422篇 |
国内免费 | 1篇 |
专业分类
5532篇 |
出版年
2024年 | 7篇 |
2023年 | 30篇 |
2022年 | 110篇 |
2021年 | 205篇 |
2020年 | 120篇 |
2019年 | 140篇 |
2018年 | 150篇 |
2017年 | 131篇 |
2016年 | 221篇 |
2015年 | 366篇 |
2014年 | 370篇 |
2013年 | 396篇 |
2012年 | 541篇 |
2011年 | 464篇 |
2010年 | 269篇 |
2009年 | 227篇 |
2008年 | 310篇 |
2007年 | 313篇 |
2006年 | 240篇 |
2005年 | 210篇 |
2004年 | 176篇 |
2003年 | 177篇 |
2002年 | 136篇 |
2001年 | 23篇 |
2000年 | 11篇 |
1999年 | 18篇 |
1998年 | 27篇 |
1997年 | 21篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 15篇 |
1993年 | 16篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 3篇 |
1989年 | 2篇 |
1988年 | 4篇 |
1987年 | 2篇 |
1986年 | 3篇 |
1984年 | 4篇 |
1983年 | 3篇 |
1982年 | 3篇 |
1981年 | 3篇 |
1979年 | 2篇 |
1976年 | 5篇 |
1973年 | 3篇 |
1972年 | 2篇 |
1971年 | 4篇 |
1969年 | 3篇 |
1968年 | 3篇 |
排序方式: 共有5532条查询结果,搜索用时 15 毫秒
101.
Pinheiro Kelly V. Thomaz Amanda Souza Bárbara Kunzler Metcalfe Victoria Anne Freire Natália Hogetop Brunetto André Tesainer de Farias Caroline Brunetto Jaeger Mariane Bambini Victorio Smith Christopher G. S. Shaw Lisa Roesler Rafael 《Molecular biology reports》2020,47(9):6817-6828
Molecular Biology Reports - A member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene) is an increasingly important target in various... 相似文献
102.
Gang Liu Rohinee Beri Amanda Mueller David W. Kamp 《Chemico-biological interactions》2010,188(2):309-318
Asbestos causes pulmonary fibrosis (asbestosis) and malignancies (bronchogenic lung cancer and mesothelioma) by mechanisms that are not fully elucidated. Accumulating evidence show that alveolar epithelial cell (AEC) apoptosis is a crucial initiating and perpetuating event in the development of pulmonary fibrosis following exposure to a wide variety of noxious stimuli, including asbestos. We review the important molecular mechanisms underlying asbestos-induced AEC apoptosis. Specifically, we focus on the role of asbestos in augmenting AEC apoptosis by the mitochondria- and p53-regulated death pathways that result from the production of iron-derived reactive oxygen species (ROS) and DNA damage. We summarize emerging evidence implicating the endoplasmic reticulum (ER) stress response in AEC apoptosis in patients with idiopathic pulmonary fibrosis (IPF), a disease with similarities to asbestosis. Finally, we discuss a recent finding that a mitochondrial oxidative DNA repair enzyme (8-oxoguanine DNA glycosylase; Ogg1) acts as a mitochondrial aconitase chaperone protein to prevent oxidant (asbestos and H2O2)-induced AEC mitochondrial dysfunction and intrinsic apoptosis. The coupling of mitochondrial Ogg1 to mitochondrial aconitase is a novel mechanism linking metabolism to mitochondrial DNA that may be important in the pathophysiologic events resulting in oxidant-induced toxicity as seen in tumors, aging, and respiratory disorders (e.g. asbestosis, IPF). Collectively, these studies are illuminating the molecular basis of AEC apoptosis following asbestos exposure that may prove useful for developing novel therapeutic strategies. Importantly, the asbestos paradigm is elucidating pathophysiologic insights into other more common pulmonary diseases, such as IPF and lung cancer, for which better therapy is required. 相似文献
103.
Numerous polypeptides and proteins form amyloid deposits in vivo or in vitro. The mechanism of amyloid formation is not well-understood particularly in the case where unstructured polypeptides assemble to form amyloid. Aromatic-aromatic interactions are known to be important in globular proteins, and the possibility that they might play a key role in amyloid formation has been raised. The results of Ala-scanning experiments on short polypeptides derived from Amylin have suggested that aromatic interactions could be particularly important for this system. Here, we examine a set of Amylin-derived polypeptides in which the single aromatic residue has been substituted with a Leu and Ala. A peptide corresponding to residues 21-29 with a Phe-23 to Leu substitution, a free N terminus, and amidated C terminus readily forms amyloid. Shorter peptides derived from the putative minimal amyloid-forming segment of Amylin, residues 22-27, also form amyloid when Phe-23 is replaced by Leu. Amyloid formation is more facile when the N terminus is deprotonated and the peptide is uncharged. Substitution of the Phe with Ala results in a peptide that is noticeably less prone to form amyloid. A peptide corresponding to residues 10-19 of human Amylin with blocked termini and the sole aromatic residue, Phe-15, substituted by Leu readily forms amyloid. A Phe-15 to Ala substitution reduces significantly the ability to form amyloid. These results indicate that an aromatic residue is not required for amyloid formation in these systems and indicates that other factors such as size, beta-sheet propensity, and hydrophobicity of the side chain in question are also important. 相似文献
104.
Theendakara V Tromp G Kuivaniemi H White PS Panchal S Cox J Winters RS Riebeling P Tost F Hoeltzenbein M Tervo TM Henn W Denniger E Krause M Koksal M Kargi S Ugurbas SH Latvala T Shearman AM Weiss JS 《Human genetics》2004,114(6):594-600
Schnyders crystalline corneal dystrophy (SCCD) is a rare autosomal dominant eye disease with a spectrum of clinical manifestations that may include bilateral corneal clouding, arcus lipoides, and anterior corneal crystalline cholesterol deposition. We have previously performed a genome-wide linkage analysis on two large Swede-Finn families and mapped the SCCD locus to a 16-cM interval between markers D1S2633 and D1S228 on chromosome 1p36. We have collected 11 additional families from Finland, Germany, Turkey, and USA to narrow the critical region for SCCD. Here, we have used haplotype analysis with densely spaced microsatellite markers in a total of 13 families to refine the candidate interval. A common disease haplotype was observed among the four Swede-Finn families indicating the presence of a founder effect. Recombination results from all 13 families refined the SCCD locus to 2.32 Mbp between markers D1S1160 and D1S1635. Within this interval, identity-by-state was present in all 13 families for two markers D1S244 and D1S3153, further refining the candidate region to 1.58 Mbp. 相似文献
105.
Introduction
One of the most important trade-offs for many animals is that between survival and reproduction. This is particularly apparent when mating increases the risk of predation, either by increasing conspicuousness, reducing mobility or inhibiting an individual''s ability to detect predators. Individuals may mitigate the risk of predation by altering their reproductive behavior (e.g. increasing anti-predator responses to reduce conspicuousness). The degree to which individuals modulate their reproductive behavior in relation to predation risk is difficult to predict because both the optimal investment in current and future reproduction (due to life-history strategies) and level of predation risk may differ between the sexes and among species. Here, we investigate the effect of increased predation risk on the reproductive behavior of dumpling squid (Euprymna tasmanica).Results
Females, but not males, showed a substantial increase in the number of inks (an anti-predator behavior) before mating commenced in the presence of a predator (sand flathead Platycephalus bassensis). However, predation risk did not affect copulation duration, the likelihood of mating, female anti-predator behavior during or after mating or male anti-predator behavior at any time.Conclusions
Inking is a common anti-predator defense in cephalopods, thought to act like a smokescreen, decoy or distraction. Female dumpling squid are probably using this form of defense in response to the increase in predation risk prior to mating. Conversely, males were undeterred by the increase in predation risk. A lack of change in these variables may occur if the benefit of completing mating outweighs the risk of predation. Prioritizing current reproduction, even under predation risk, can occur when the chance of future reproduction is low, there is substantial energetic investment into mating, or the potential fitness payoffs of mating are high. 相似文献106.
107.
Nindl BC Scofield DE Strohbach CA Centi AJ Evans RK Yanovich R Moran DS 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(Z2):S73-S81
Insulin-like growth factor 1 (IGF-I) is a robust metabolic and anabolic biomarker that has been demonstrated to be reflective of military training-induced body composition changes and influenced by initial aerobic fitness level. Greater mechanistic insight into the IGF-I response to physical training can potentially be gleaned by also examining other regulatory factors that influence IGF-I biological activity (i.e., insulin-like growth factor-binding proteins [IGFBPs] and inflammatory cytokine responses). The purpose of this study was to assess the influence of sex and initial fitness level on the IGF-I and inflammatory cytokine response to gender-integrated Israeli Defense Forces (IDF) basic combat training (BCT). Recruits (29 men, 19.1 ± 1.3 years; 93 women, 18.8 ± 0.6 years) were recruited from a 4-month gender-integrated BCT of the IDF. Blood was drawn and assayed for total IGF-I, free IGF-I, IGFBPs 1-6, tumor necrosis factor alpha (TNF-α), interleukin 6, and interleukin 1 beta. Body composition was determined via a 4-site skinfold (biceps, triceps, suprailiac, and subscapular) equation. Physical performance was assessed via a maximum volume of oxygen consumption (V[Combining Dot Above]O?max) test using a treadmill protocol. All measures were obtained pre- and posttraining. A 2-way (sex × time) analysis of variance was used to test for statistical differences (p ≤ 0.05). Additionally, subjects were further partitioned (men and women separately) by tertiles of initial V[Combining Dot Above]O?max to assess the influence of initial fitness level on the IGF-I system and inflammatory cytokine responses to physical training. Pearson product moment correlational analysis was also used to examine relationships between percent changes in blood measures and physical performance and body composition changes. All data are presented as mean ± SE. Time effects were observed only for total IGF-I, IGFBP-2, TNF-α, V[Combining Dot Above]O?max, fat-free mass, and fat mass. The only significant (p ≤ 0.05) correlations observed for percent changes were in men between total IGF-I and V[Combining Dot Above]O?max (r = 0.49) and body mass (r = -0.42) During gender-integrated Israeli Army BCT, men and women generally respond in a similar fashion with regard to blood measures (IGF-I system and inflammatory cytokines) and V[Combining Dot Above]O?max. Initial fitness level only influenced the IGF-I response to training in women. Although the training-induced changes in total IGF-I (increase), IGFBP-2 (decrease), and TNF-α (decrease) are all indicative of an enhanced circulating anabolic milieu, only total IGF-I for the men was correlated with body composition and fitness improvements. 相似文献
108.
Alexandra K. Fraik Mark J. Margres Brendan Epstein Soraia Barbosa Menna Jones Sarah Hendricks Barbara Schönfeld Amanda R. Stahlke Anne Veillet Rodrigo Hamede Hamish McCallum Elisa Lopez-Contreras Samantha J. Kallinen Paul A. Hohenlohe Joanna L. Kelley Andrew Storfer 《Evolution; international journal of organic evolution》2020,74(7):1392-1408
Landscape genomics studies focus on identifying candidate genes under selection via spatial variation in abiotic environmental variables, but rarely by biotic factors (i.e., disease). The Tasmanian devil (Sarcophilus harrisii) is found only on the environmentally heterogeneous island of Tasmania and is threatened with extinction by a transmissible cancer, devil facial tumor disease (DFTD). Devils persist in regions of long-term infection despite epidemiological model predictions of species’ extinction, suggesting possible adaptation to DFTD. Here, we test the extent to which spatial variation and genetic diversity are associated with the abiotic environment (i.e., climatic variables, elevation, vegetation cover) and/or DFTD. We employ genetic-environment association analyses using 6886 SNPs from 3287 individuals sampled pre- and post-disease arrival across the devil's geographic range. Pre-disease, we find significant correlations of allele frequencies with environmental variables, including 365 unique loci linked to 71 genes, suggesting local adaptation to abiotic environment. The majority of candidate loci detected pre-DFTD are not detected post-DFTD arrival. Several post-DFTD candidate loci are associated with disease prevalence and were in linkage disequilibrium with genes involved in tumor suppression and immune response. Loss of apparent signal of abiotic local adaptation post-disease suggests swamping by strong selection resulting from the rapid onset of DFTD. 相似文献
109.
Amanda D. Melin Brooke E. Crowley Shaun T. Brown Patrick V. Wheatley Gillian L. Moritz Fred Tuh Yit Yu Henry Bernard Donald J. DePaolo Andrew D. Jacobson Nathaniel J. Dominy 《American journal of physical anthropology》2014,154(4):633-643
Calcium stable isotope ratios are hypothesized to vary as a function of trophic level. This premise raises the possibility of using calcium stable isotope ratios to study the dietary behaviors of fossil taxa and to test competing hypotheses on the adaptive origins of euprimates. To explore this concept, we measured the stable isotope composition of contemporary mammals in northern Borneo and northwestern Costa Rica, two communities with functional or phylogenetic relevance to primate origins. We found that bone collagen δ13C and δ15N values could differentiate trophic levels in each assemblage, a result that justifies the use of these systems to test the predicted inverse relationship between bioapatite δ13C and δ44Ca values. As expected, taxonomic carnivores (felids) showed a combination of high δ13C and low δ44Ca values; however, the δ44Ca values of other faunivores were indistinguishable from those of primary consumers. We suggest that the trophic insensitivity of most bioapatite δ44Ca values is attributable to the negligible calcium content of arthropod prey. Although the present results are inconclusive, the tandem analysis of δ44Ca and δ13C values in fossils continues to hold promise for informing paleodietary studies and we highlight this potential by drawing attention to the stable isotope composition of the Early Eocene primate Cantius. Am J Phys Anthropol 154:633–643, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
110.
Amanda E. Elledge Clive A. McAlpine Peter J. Murray Iain J. Gordon 《Biological invasions》2013,15(7):1523-1535
Feral pigs (Sus scrofa) occupy many different habitats worldwide. Their rooting foraging behaviour poses a serious threat to biodiversity as the resulting soil disturbance alters ecosystem structure and function. Understanding what characteristics are important in selecting rooting locations can be used to predict the impact of pigs on ecosystems. We investigated patch selection for rooting by feral pigs at two spatial scales: (1) habitat variables at a site level, and (2) dependency between observations in a spatial context. Seasonal influences on the modelled environmental variables were also examined. We applied a generalised linear modelling approach and model-averaging to explain the relative importance of variables, as measured by the standardised parameter estimates and unconditional variance. Soil texture, rock cover, soil compaction and sand texture were important explanatory variables in the presence of pig rooting. Soil compaction and distance to roads had a negative influence. The highest ranking model included seven explanatory variables with a 41 % chance that this is the Kullback–Leibler best model. Six of the 128 candidate models were in the 95 % confidence set indicating low model uncertainty. Although no differences in pig rootings were detected between seasons, most rooting (65.7 %) occurred during the dry season with soil and sand texture having the strongest effect. This study highlights how pig control programmes can focus limited resources on either the strategic positioning of control devices (e.g., traps and baits) to either reduce the number of pigs or help prioritise habitats of high conservation value for protection (e.g., exclusion fencing). 相似文献