全文获取类型
收费全文 | 4838篇 |
免费 | 458篇 |
出版年
2024年 | 7篇 |
2023年 | 22篇 |
2022年 | 22篇 |
2021年 | 170篇 |
2020年 | 97篇 |
2019年 | 115篇 |
2018年 | 111篇 |
2017年 | 107篇 |
2016年 | 173篇 |
2015年 | 307篇 |
2014年 | 312篇 |
2013年 | 338篇 |
2012年 | 450篇 |
2011年 | 461篇 |
2010年 | 275篇 |
2009年 | 244篇 |
2008年 | 316篇 |
2007年 | 300篇 |
2006年 | 268篇 |
2005年 | 244篇 |
2004年 | 227篇 |
2003年 | 200篇 |
2002年 | 170篇 |
2001年 | 26篇 |
2000年 | 21篇 |
1999年 | 17篇 |
1998年 | 34篇 |
1997年 | 19篇 |
1996年 | 8篇 |
1995年 | 15篇 |
1994年 | 11篇 |
1993年 | 10篇 |
1992年 | 11篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 17篇 |
1988年 | 5篇 |
1987年 | 13篇 |
1985年 | 5篇 |
1984年 | 8篇 |
1982年 | 10篇 |
1981年 | 13篇 |
1980年 | 9篇 |
1979年 | 5篇 |
1978年 | 11篇 |
1977年 | 5篇 |
1975年 | 6篇 |
1974年 | 4篇 |
1973年 | 9篇 |
1968年 | 6篇 |
排序方式: 共有5296条查询结果,搜索用时 31 毫秒
991.
Glutamate mediates most excitatory synaptic transmission in the brain. Synaptic strength at glutamatergic synapses shows a remarkable degree of use-dependent plasticity and such modifications may represent a physiological correlate to learning and memory. Glutamate receptors and downstream enzymes are organized at synapses by cytoskeletal proteins containing multiple protein-interacting domains. Recent studies demonstrate that these 'scaffolding' proteins within the postsynaptic specialization have the capacity to promote synaptic maturation, influence synapse size, and modulate glutamate receptor function. 相似文献
992.
Miller EN Rupp AL Lindberg MK Wiese TJ 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2005,140(3):513-520
L-fucose (fucose) is a monosaccharide normally present in mammals and is unique in being the only levorotatory sugar that can be synthesized and utilized by mammals. The metabolism of fucose is incompletely understood, but fucose can be synthesized de novo or salvaged. The utilization of fucose in the salvage pathway begins with phosphorylation by fucokinase. As part of an investigation of fucose metabolism in normal and disease states, we began an investigation of this enzyme. In this report, we present the tissue distribution of the enzyme in rat and mouse. The highest amount of activity was present in brain of both species. Some activity was found in all tissues examined (liver, kidney, heart, lung, spleen, brain, muscle, thymus, white adipose, testes, eye, aorta, small intestine, and submaxillary gland). Very low levels were found in small intestine. Varying levels in the tissues seems most likely to be the result of varying amounts of fucokinase protein as no difference in the Km values of crude enzyme could be shown. Protein-bound fucose levels were determined using the L-cysteine-phenol-sulfuric acid (CPS) assay. There is not a good correlation between fucokinase activity and protein-bound fucose, suggesting some tissues are more active in synthesis of fucose than others. 相似文献
993.
Neuropeptide Y-mediated inhibition of proopiomelanocortin neurons in the arcuate nucleus shows enhanced desensitization in ob/ob mice 总被引:11,自引:0,他引:11
NPY and alphaMSH are expressed in distinct neurons in the arcuate nucleus of the hypothalamus, where alphaMSH decreases and NPY increases food intake and body weight. Here we use patch-clamp electrophysiology from GFP-labeled POMC and NPY neurons to demonstrate that NPY strongly hyperpolarized POMC neurons through the Y1R-mediated activation of GIRK channels, while the alphaMSH analog, MTII, had no effect on activity of NPY neurons. While initially NPY had similar effects on POMC neurons derived from ob/ob mice, further studies revealed a significant increase in desensitization of the NPY-induced currents in POMC neurons from ob/ob mice. This increase in desensitization was specific to NPY, as GABA(B) and microOR agonists showed unaltered desensitization in POMC neurons from ob/ob mice. These data reveal an intricate and asymmetric interplay between NPY and POMC neurons in the hypothalamus and have important implications for the delineation of the neural circuits that regulate feeding behavior. 相似文献
994.
Elyse C. Johnson Aaron M. Sullivan 《Ethology : formerly Zeitschrift fur Tierpsychologie》2014,120(7):672-680
Prey species may reduce the likelihood of injury or death by engaging in defensive behavior but often incur costs related to decreased foraging success or efficiency. To lessen these costs, prey may adjust the intensity or type of antipredator behavior according to the nature of the perceived threat. We evaluated the potential for threat‐sensitive responses by Allegheny Mountain dusky salamanders (Desmognathus ochrophaeus) exposed to chemical stimuli associated with predation by asking three questions: (1) Do individual D. ochrophaeus respond to chemical cues in a threat‐sensitive manner? (2) Do salamanders exhibit the same pattern of behavioral response while foraging? and (3) Is foraging efficiency reduced when focal individuals are exposed to stimuli from predators or predation events? In our first experiment, we evaluated salamander chemosensory movements (nose‐taps), locomotor activity (steps), and edge behavior in response to chemical stimuli from disturbed and injured conspecifics as well as predatory Gyrinophilus porphyriticus and found that individual D. ochrophaeus show a significant graded increase in nose‐taps when exposed to cues from conspecifics and a reduction in activity when exposed to the predator. In our second experiment, we again observed salamander responses to the same chemical stimuli but in this instance added five Drosophila prey to the test dishes. We found that salamanders exhibited a similar pattern of response to the chemical stimuli in the presence of prey, showing a graded increase in nose‐taps to cues from conspecifics and a reduction in activity when exposed to the predator. However, foraging efficiency (i.e. the proportion of successful strikes) did not vary significantly among treatments. Our data show that individual D. ochrophaeus detect and differentially respond to chemical stimuli associated with predation, but do not significantly reduce foraging efficiency. Overall, the type and relative intensity of these responses is largely unaffected by the presence of potential prey. 相似文献
995.
Developmental refinement of hair cell synapses tightens the coupling of Ca2+ influx to exocytosis 下载免费PDF全文
Aaron B Wong Mark A Rutherford Mantas Gabrielaitis Tina Pangršič Fabian Göttfert Thomas Frank Susann Michanski Stefan Hell Fred Wolf Carolin Wichmann Tobias Moser 《The EMBO journal》2014,33(3):247-264
Cochlear inner hair cells (IHCs) develop from pre‐sensory pacemaker to sound transducer. Here, we report that this involves changes in structure and function of the ribbon synapses between IHCs and spiral ganglion neurons (SGNs) around hearing onset in mice. As synapses matured they changed from holding several small presynaptic active zones (AZs) and apposed postsynaptic densities (PSDs) to one large AZ/PSD complex per SGN bouton. After the onset of hearing (i) IHCs had fewer and larger ribbons; (ii) CaV1.3 channels formed stripe‐like clusters rather than the smaller and round clusters at immature AZs; (iii) extrasynaptic CaV1.3‐channels were selectively reduced, (iv) the intrinsic Ca2+ dependence of fast exocytosis probed by Ca2+ uncaging remained unchanged but (v) the apparent Ca2+ dependence of exocytosis linearized, when assessed by progressive dihydropyridine block of Ca2+ influx. Biophysical modeling of exocytosis at mature and immature AZ topographies suggests that Ca2+ influx through an individual channel dominates the [Ca2+] driving exocytosis at each mature release site. We conclude that IHC synapses undergo major developmental refinements, resulting in tighter spatial coupling between Ca2+ influx and exocytosis. 相似文献
996.
Dustin P. Patterson Min Su Titus M. Franzmann Aaron Sciore Georgios Skiniotis E. Neil G. Marsh 《Protein science : a publication of the Protein Society》2014,23(2):190-199
The design of proteins that self-assemble into well-defined, higher order structures is an important goal that has potential applications in synthetic biology, materials science, and medicine. We previously designed a two-component protein system, designated A-(+) and A-(−), in which self-assembly is mediated by complementary electrostatic interactions between two coiled-coil sequences appended to the C-terminus of a homotrimeric enzyme with C3 symmetry. The coiled-coil sequences are attached through a short, flexible spacer sequence providing the system with a high degree of conformational flexibility. Thus, the primary constraint guiding which structures the system may assemble into is the symmetry of the protein building block. We have now characterized the properties of the self-assembling system as a whole using native gel electrophoresis and analytical ultracentrifugation (AUC) and the properties of individual assemblies using cryo-electron microscopy (EM). We show that upon mixing, A-(+) and A-(−) form only six different complexes in significant concentrations. The three predominant complexes have hydrodynamic properties consistent with the formation of heterodimeric, tetrahedral, and octahedral protein cages. Cryo-EM of size-fractionated material shows that A-(+) and A-(−) form spherical particles with diameters appropriate for tetrahedral or octahedral protein cages. The particles varied in diameter in an almost continuous manner suggesting that their structures are extremely flexible. 相似文献
997.
Michael Sproviero Anne M.R. Verwey Katherine M. Rankin Aaron A. Witham Dmitriy V. Soldatov Richard A. Manderville Mostafa I. Fekry Shana J. Sturla Purshotam Sharma Stacey D. Wetmore 《Nucleic acids research》2014,42(21):13405-13421
Chemical mutagens with an aromatic ring system may be enzymatically transformed to afford aryl radical species that preferentially react at the C8-site of 2′-deoxyguanosine (dG). The resulting carbon-linked C8-aryl-dG adduct possesses altered biophysical and genetic coding properties compared to the precursor nucleoside. Described herein are structural and in vitro mutagenicity studies of a series of fluorescent C8-aryl-dG analogues that differ in aryl ring size and are representative of authentic DNA adducts. These structural mimics have been inserted into a hotspot sequence for frameshift mutations, namely, the reiterated G3-position of the NarI sequence within 12mer (NarI(12)) and 22mer (NarI(22)) oligonucleotides. In the NarI(12) duplexes, the C8-aryl-dG adducts display a preference for adopting an anti-conformation opposite C, despite the strong syn preference of the free nucleoside. Using the NarI(22) sequence as a template for DNA synthesis in vitro, mutagenicity of the C8-aryl-dG adducts was assayed with representative high-fidelity replicative versus lesion bypass Y-family DNA polymerases, namely, Escherichia coli pol I Klenow fragment exo− (Kf−) and Sulfolobus solfataricus P2 DNA polymerase IV (Dpo4). Our experiments provide a basis for a model involving a two-base slippage and subsequent realignment process to relate the miscoding properties of C-linked C8-aryl-dG adducts with their chemical structures. 相似文献
998.
High‐Resolution Molecular Validation of Self‐Renewal and Spontaneous Differentiation in Clinical‐Grade Adipose‐Tissue Derived Human Mesenchymal Stem Cells 下载免费PDF全文
Amel Dudakovic Emily Camilleri Scott M. Riester Eric A. Lewallen Sergiy Kvasha Xiaoyue Chen Darcie J. Radel Jarett M. Anderson Asha A. Nair Jared M. Evans Aaron J. Krych Jay Smith David R. Deyle Janet L. Stein Gary S. Stein Hee‐Jeong Im Simon M. Cool Jennifer J. Westendorf Sanjeev Kakar Allan B. Dietz Andre J. van Wijnen 《Journal of cellular biochemistry》2014,115(10):1816-1828
999.
Francisco Amaro Aaron P. Turkewitz Ana Martín-González Juan Carlos Gutiérrez 《Biometals》2014,27(1):195-205
1000.
Micaela Martinez-Bakker Kevin M. Bakker Aaron A. King Pejman Rohani 《Proceedings. Biological sciences / The Royal Society》2014,281(1783)
More than a century of ecological studies have demonstrated the importance of demography in shaping spatial and temporal variation in population dynamics. Surprisingly, the impact of seasonal recruitment on infectious disease systems has received much less attention. Here, we present data encompassing 78 years of monthly natality in the USA, and reveal pronounced seasonality in birth rates, with geographical and temporal variation in both the peak birth timing and amplitude. The timing of annual birth pulses followed a latitudinal gradient, with northern states exhibiting spring/summer peaks and southern states exhibiting autumn peaks, a pattern we also observed throughout the Northern Hemisphere. Additionally, the amplitude of United States birth seasonality was more than twofold greater in southern states versus those in the north. Next, we examined the dynamical impact of birth seasonality on childhood disease incidence, using a mechanistic model of measles. Birth seasonality was found to have the potential to alter the magnitude and periodicity of epidemics, with the effect dependent on both birth peak timing and amplitude. In a simulation study, we fitted an susceptible-exposed-infected-recovered model to simulated data, and demonstrated that ignoring birth seasonality can bias the estimation of critical epidemiological parameters. Finally, we carried out statistical inference using historical measles incidence data from New York City. Our analyses did not identify the predicted systematic biases in parameter estimates. This may be owing to the well-known frequency-locking between measles epidemics and seasonal transmission rates, or may arise from substantial uncertainty in multiple model parameters and estimation stochasticity. 相似文献