全文获取类型
收费全文 | 3723篇 |
免费 | 373篇 |
国内免费 | 4篇 |
出版年
2023年 | 14篇 |
2022年 | 16篇 |
2021年 | 48篇 |
2020年 | 45篇 |
2019年 | 64篇 |
2018年 | 49篇 |
2017年 | 54篇 |
2016年 | 82篇 |
2015年 | 132篇 |
2014年 | 177篇 |
2013年 | 186篇 |
2012年 | 263篇 |
2011年 | 312篇 |
2010年 | 187篇 |
2009年 | 161篇 |
2008年 | 224篇 |
2007年 | 260篇 |
2006年 | 199篇 |
2005年 | 214篇 |
2004年 | 178篇 |
2003年 | 175篇 |
2002年 | 175篇 |
2001年 | 54篇 |
2000年 | 29篇 |
1999年 | 45篇 |
1998年 | 36篇 |
1997年 | 29篇 |
1996年 | 25篇 |
1995年 | 25篇 |
1994年 | 23篇 |
1993年 | 39篇 |
1992年 | 23篇 |
1991年 | 34篇 |
1990年 | 28篇 |
1989年 | 26篇 |
1988年 | 34篇 |
1987年 | 26篇 |
1986年 | 33篇 |
1985年 | 27篇 |
1984年 | 32篇 |
1983年 | 24篇 |
1982年 | 29篇 |
1981年 | 35篇 |
1980年 | 24篇 |
1979年 | 21篇 |
1978年 | 16篇 |
1977年 | 20篇 |
1976年 | 17篇 |
1974年 | 21篇 |
1973年 | 18篇 |
排序方式: 共有4100条查询结果,搜索用时 15 毫秒
51.
52.
Jip J. C. Ramakers Phillip Gienapp Marcel E. Visser 《Evolution; international journal of organic evolution》2019,73(2):175-187
Phenotypic plasticity is an important mechanism for populations to respond to fluctuating environments, yet may be insufficient to adapt to a directionally changing environment. To study whether plasticity can evolve under current climate change, we quantified selection and genetic variation in both the elevation (RNE) and slope (RNS) of the breeding time reaction norm in a long‐term (1973–2016) study population of great tits (Parus major). The optimal RNE (the caterpillar biomass peak date regressed against the temperature used as cue by great tits) changed over time, whereas the optimal RNS did not. Concordantly, we found strong directional selection on RNE, but not RNS, of egg‐laying date in the second third of the study period; this selection subsequently waned, potentially due to increased between‐year variability in optimal laying dates. We found individual and additive genetic variation in RNE but, contrary to previous studies on our population, not in RNS. The predicted and observed evolutionary change in RNE was, however, marginal, due to low heritability and the sex limitation of laying date. We conclude that adaptation to climate change can only occur via micro‐evolution of RNE, but this will necessarily be slow and potentially hampered by increased variability in phenotypic optima. 相似文献
53.
Birds'' eggshells are renowned for their striking colours and varied patterns. Although often considered exceptionally diverse, we report that avian eggshell coloration, sampled here across the full phylogenetic diversity of birds, occupies only 0.08–0.10% of the avian perceivable colour space. The concentrations of the two known tetrapyrrole eggshell pigments (protoporphyrin and biliverdin) are generally poor predictors of colour, both intra- and interspecifically. Here, we show that the constrained diversity of eggshell coloration can be accurately predicted by colour mixing models based on the relative contribution of both pigments and we demonstrate that the models'' predictions can be improved by accounting for the reflectance of the eggshell''s calcium carbonate matrix. The establishment of these proximate links between pigmentation and colour will enable future tests of hypotheses on the functions of perceived avian eggshell colours that depend on eggshell chemistry. More generally, colour mixing models are not limited to avian eggshell colours but apply to any natural colour. Our approach illustrates how modelling can aid the understanding of constraints on phenotypic diversity. 相似文献
54.
Satyan Sharma Brian N. Kim Phillip J. Stansfeld Mark S. P. Sansom Manfred Lindau 《PloS one》2015,10(12)
The resemblance of lipid membrane models to physiological membranes determines how well molecular dynamics (MD) simulations imitate the dynamic behavior of cell membranes and membrane proteins. Physiological lipid membranes are composed of multiple types of phospholipids, and the leaflet compositions are generally asymmetric. Here we describe an approach for self-assembly of a Coarse-Grained (CG) membrane model with physiological composition and leaflet asymmetry using the MARTINI force field. An initial set-up of two boxes with different types of lipids according to the leaflet asymmetry of mammalian cell membranes stacked with 0.5 nm overlap, reliably resulted in the self-assembly of bilayer membranes with leaflet asymmetry resembling that of physiological mammalian cell membranes. Self-assembly in the presence of a fragment of the plasma membrane protein syntaxin 1A led to spontaneous specific positioning of phosphatidylionositol(4,5)bisphosphate at a positively charged stretch of syntaxin consistent with experimental data. An analogous approach choosing an initial set-up with two concentric shells filled with different lipid types results in successful assembly of a spherical vesicle with asymmetric leaflet composition. Self-assembly of the vesicle in the presence of the synaptic vesicle protein synaptobrevin 2 revealed the correct position of the synaptobrevin transmembrane domain. This is the first CG MD method to form a membrane with physiological lipid composition as well as leaflet asymmetry by self-assembly and will enable unbiased studies of the incorporation and dynamics of membrane proteins in more realistic CG membrane models. 相似文献
55.
Proteomic analysis and functional characterization of mouse brain mitochondria during aging reveal alterations in energy metabolism 下载免费PDF全文
Kelly L. Stauch Phillip R. Purnell Lance M. Villeneuve Howard S. Fox 《Proteomics》2015,15(9):1574-1586
Mitochondria are the main cellular source of reactive oxygen species and are recognized as key players in several age‐associated disorders and neurodegeneration. Their dysfunction has also been linked to cellular aging. Additionally, mechanisms leading to the preservation of mitochondrial function promote longevity. In this study we investigated the proteomic and functional alterations in brain mitochondria isolated from mature (5 months old), old (12 months old), and aged (24 months old) mice as determinants of normal “healthy” aging. Here the global changes concomitant with aging in the mitochondrial proteome of mouse brain analyzed by quantitative mass‐spectrometry based super‐SILAC identified differentially expressed proteins involved in several metabolic pathways including glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Despite these changes, the bioenergetic function of these mitochondria was preserved. Overall, this data indicates that proteomic changes during aging may compensate for functional defects aiding in preservation of mitochondrial function. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the data set identifier PXD001370 ( http://proteomecentral.proteomexchange.org/dataset/PXD001370 ). 相似文献
56.
Andreas Bergmann Phillip Trefz Sina Fischer Klaus Klepik Gudrun Walter Markus Steffens Mario Ziller Jochen K. Schubert Petra Reinhold Heike K?hler Wolfram Miekisch 《PloS one》2015,10(4)
Mycobacterium avium ssp. paratuberculosis (MAP) is the causative agent of a chronic enteric disease of ruminants. Available diagnostic tests are complex and slow. In vitro, volatile organic compound (VOC) patterns emitted from MAP cultures mirrored bacterial growth and enabled distinction of different strains. This study was intended to determine VOCs in vivo in the controlled setting of an animal model. VOCs were pre-concentrated from breath and feces of 42 goats (16 controls and 26 MAP-inoculated animals) by means of needle trap microextraction (breath) and solid phase microextraction (feces) and analyzed by gas chromatography/ mass spectrometry. Analyses were performed 18, 29, 33, 41 and 48 weeks after inoculation. MAP-specific antibodies and MAP-specific interferon-γ-response were determined from blood. Identities of all marker-VOCs were confirmed through analysis of pure reference substances. Based on detection limits in the high pptV and linear ranges of two orders of magnitude more than 100 VOCs could be detected in breath and in headspace over feces. Twenty eight substances differed between inoculated and non-inoculated animals. Although patterns of most prominent substances such as furans, oxygenated substances and hydrocarbons changed in the course of infection, differences between inoculated and non-inoculated animals remained detectable at any time for 16 substances in feces and 3 VOCs in breath. Differences of VOC concentrations over feces reflected presence of MAP bacteria. Differences in VOC profiles from breath were linked to the host response in terms of interferon-γ-response. In a perspective in vivo analysis of VOCs may help to overcome limitations of established tests. 相似文献
57.
Carmen S. M. Yong Janelle Sharkey Belinda Duscio Ben Venville Wei-Zen Wei Richard F. Jones Clare Y. Slaney Gisela Mir Arnau Anthony T. Papenfuss Jan Schr?der Phillip K. Darcy Michael H. Kershaw 《PloS one》2015,10(9)
The development of antigen-targeted therapeutics is dependent on the preferential expression of tumor-associated antigens (TAA) at targetable levels on the tumor. Tumor-associated antigens can be generated de novo or can arise from altered expression of normal basal proteins, such as the up-regulation of human epidermal growth factor receptor 2 (Her2/ErbB2). To properly assess the development of Her2 therapeutics in an immune tolerant model, we previously generated a transgenic mouse model in which expression of the human Her2 protein was present in both the brain and mammary tissue. This mouse model has facilitated the development of Her2 targeted therapies in a clinically relevant and suitable model. While heterozygous Her2+/- mice appear to develop in a similar manner to wild type mice (Her2-/-), it has proven difficult to generate homozygous Her2+/+ mice, potentially due to embryonic lethality. In this study, we performed whole genome sequencing to determine if the integration site of the Her2 transgene was responsible for this lethality. Indeed, we report that the Her2 transgene had integrated into the Pds5b (precocious dissociation of sisters) gene on chromosome 5, as a 162 copy concatemer. Furthermore, our findings demonstrate that Her2+/+ mice, similar to Pds5b-/- mice, are embryonic lethal and confirm the necessity for Pds5b in embryonic development. This study confirms the value of whole genome sequencing in determining the integration site of transgenes to gain insight into associated phenotypes. 相似文献
58.
A new record of a sauropodomorph dinosaur is here described from the Middle Jurassic (Aalenian) Saltwick Formation of Whitby (Yorkshire), UK. A single caudal vertebra represents an early sauropodomorph and signifies the earliest recognised eusauropod dinosaur from the United Kingdom. The absence of pleurocoels and a narrow, dorsoventrally deep, but craniocaudally short centrum, suggests a primitive sauropodomorph. Distinct spinopostzygopophyseal laminae rise from the lateral margins of the postzygapophyses and pass caudally along what remains of the neural spine, a character unique to a subgroup of sauropods that includes Barapasaurus, Omeisaurus and other neosauropods and eusauropods. The lack of phylogenetically robust characters in sauropod caudal vertebrae usually makes it difficult to establish affinities, but the absence of mild procoely excludes this specimen from both Diplodocoidea and Lithostrotia. The vertebra cannot be further distinguished from those of a wide range of basal sauropods, cetiosaurids and basal macronarians. However, this plesiomorphic vertebra still signifies the earliest stratigraphic occurrence for a British sauropod dinosaur. 相似文献
59.
60.
Martina Sonego Michelle Oberoi Jake Stoddart Sangeetha Gajendra Rita Hendricusdottir Fazal Oozeer Daniel C. Worth Carl Hobbs Britta J. Eickholt Phillip R. Gordon-Weeks Patrick Doherty Giovanna Lalli 《PloS one》2015,10(5)
After birth, stem cells in the subventricular zone (SVZ) generate neuroblasts that migrate along the rostral migratory stream (RMS) to become interneurons in the olfactory bulb (OB). This migration is crucial for the proper integration of newborn neurons in a pre-existing synaptic network and is believed to play a key role in infant human brain development. Many regulators of neuroblast migration have been identified; however, still very little is known about the intracellular molecular mechanisms controlling this process. Here, we have investigated the function of drebrin, an actin-binding protein highly expressed in the RMS of the postnatal mammalian brain. Neuroblast migration was monitored both in culture and in brain slices obtained from electroporated mice by time-lapse spinning disk confocal microscopy. Depletion of drebrin using distinct RNAi approaches in early postnatal mice affects neuroblast morphology and impairs neuroblast migration and orientation in vitro and in vivo. Overexpression of drebrin also impairs migration along the RMS and affects the distribution of neuroblasts at their final destination, the OB. Drebrin phosphorylation on Ser142 by Cyclin-dependent kinase 5 (Cdk5) has been recently shown to regulate F-actin-microtubule coupling in neuronal growth cones. We also investigated the functional significance of this phosphorylation in RMS neuroblasts using in vivo postnatal electroporation of phosphomimetic (S142D) or non-phosphorylatable (S142A) drebrin in the SVZ of mouse pups. Preventing or mimicking phosphorylation of S142 in vivo caused similar effects on neuroblast dynamics, leading to aberrant neuroblast branching. We conclude that drebrin is necessary for efficient migration of SVZ-derived neuroblasts and propose that regulated phosphorylation of drebrin on S142 maintains leading process stability for polarized migration along the RMS, thus ensuring proper neurogenesis. 相似文献