全文获取类型
收费全文 | 1727篇 |
免费 | 172篇 |
出版年
2022年 | 21篇 |
2021年 | 45篇 |
2020年 | 17篇 |
2019年 | 22篇 |
2018年 | 30篇 |
2017年 | 35篇 |
2016年 | 33篇 |
2015年 | 88篇 |
2014年 | 62篇 |
2013年 | 72篇 |
2012年 | 94篇 |
2011年 | 116篇 |
2010年 | 65篇 |
2009年 | 68篇 |
2008年 | 77篇 |
2007年 | 55篇 |
2006年 | 51篇 |
2005年 | 58篇 |
2004年 | 62篇 |
2003年 | 63篇 |
2002年 | 45篇 |
2001年 | 28篇 |
2000年 | 39篇 |
1999年 | 45篇 |
1998年 | 16篇 |
1997年 | 19篇 |
1996年 | 20篇 |
1995年 | 14篇 |
1994年 | 16篇 |
1993年 | 17篇 |
1992年 | 34篇 |
1991年 | 24篇 |
1990年 | 29篇 |
1989年 | 28篇 |
1988年 | 24篇 |
1987年 | 27篇 |
1986年 | 22篇 |
1985年 | 16篇 |
1984年 | 15篇 |
1983年 | 26篇 |
1982年 | 21篇 |
1981年 | 17篇 |
1980年 | 16篇 |
1979年 | 16篇 |
1978年 | 14篇 |
1977年 | 15篇 |
1974年 | 12篇 |
1973年 | 18篇 |
1972年 | 15篇 |
1970年 | 11篇 |
排序方式: 共有1899条查询结果,搜索用时 15 毫秒
151.
This study is concerned with reconciling theoretical modelling of the fluid flow in the airway surface liquid with experimental
visualisation of tracer transport in human airway epithelial cultures. The airways are covered by a dense mat of cilia of
length ∼ 6 μm beating in a watery periciliary liquid (PCL). Above this there is a layer of viscoelastic mucus which traps
inhaled pathogens. Cilia propel mucus along the airway towards the trachea and mouth. Theoretical analyses of the beat cycle
smithd, fulb predict small transport of PCL compared with mucus, based on the assumption that the epithelium is impermeable
to fluid. However, an experimental study coord indicates nearly equal transport of PCL and mucus. Building on existing understanding
of steady advection-diffusion in the ASL (Blake and Gaffney, 2001; Mitran,2004) numerical simulation of an advection-diffusion
model of tracer transport is used to test several proposed flow profiles and to test the importance of oscillatory shearing
caused by the beating cilia. A mechanically derived oscillatory flow with very low mean transport of PCL results in relatively
little ‘smearing’ of the tracer pulses. Other effects such as mixing between the PCL and mucus, and significant transport
in the upper part of the PCL above the cilia tips are tested and result in still closer transport, with separation between
the tracer pulses in the two layers being less than 9%. Furthermore, experimental results may be replicated to a very high
degree of accuracy if mean transport of PCL is only 50% of mucus transport, significantly less than the mean PCL transport
first inferred on the basis of experimental results. 相似文献
152.
We discuss in detail techniques for modelling flows due to finite and infinite arrays of beating cilia. An efficient technique,
based on concepts from previous ‘singularity models’ is described, that is accurate in both near and far-fields. Cilia are
modelled as curved slender ellipsoidal bodies by distributing Stokeslet and potential source dipole singularities along their
centrelines, leading to an integral equation that can be solved using a simple and efficient discretisation. The computed
velocity on the cilium surface is found to compare favourably with the boundary condition. We then present results for two
topics of current interest in biology. 1) We present the first theoretical results showing the mechanism by which rotating
embryonic nodal cilia produce a leftward flow by a ‘posterior tilt,’ and track particle motion in an array of three simulated
nodal cilia. We find that, contrary to recent suggestions, there is no continuous layer of negative fluid transport close
to the ciliated boundary. The mean leftward particle transport is found to be just over 1 μm/s, within experimentally measured
ranges. We also discuss the accuracy of models that represent the action of cilia by steady rotlet arrays, in particular,
confirming the importance of image systems in the boundary in establishing the far-field fluid transport. Future modelling
may lead to understanding of the mechanisms by which morphogen gradients or mechanosensing cilia convert a directional flow
to asymmetric gene expression. 2) We develop a more complex and detailed model of flow patterns in the periciliary layer of
the airway surface liquid. Our results confirm that shear flow of the mucous layer drives a significant volume of periciliary
liquid in the direction of mucus transport even during the recovery stroke of the cilia. Finally, we discuss the advantages
and disadvantages of the singularity technique and outline future theoretical and experimental developments required to apply
this technique to various other biological problems, particularly in the reproductive system. 相似文献
153.
McKinnon LR Ball TB Wachihi C McLaren PJ Waruk JL Mao X Ramdahin S Anzala AO Kamene J Luo M Fowke KR Plummer FA 《Journal of immunology (Baltimore, Md. : 1950)》2007,178(6):3750-3756
HIV diversity may limit the breadth of vaccine coverage due to epitope sequence differences between strains. Although amino acid substitutions within CD8(+) T cell HIV epitopes can result in complete or partial abrogation of responses, this has primarily been demonstrated in effector CD8(+) T cells. In an HIV-infected Kenyan cohort, we demonstrate that the cross-reactivity of HIV epitope variants differs dramatically between overnight IFN-gamma and longer-term proliferation assays. For most epitopes, particular variants (not the index peptide) were preferred in proliferation in the absence of corresponding overnight IFN-gamma responses and in the absence of the variant in the HIV quasispecies. Most proliferating CD8(+) T cells were polyfunctional via cytokine analyses. A trend to positive correlation was observed between proliferation (but not IFN-gamma) and CD4 counts. We present findings relevant to the assessment of HIV vaccine candidates and toward a better understanding of how viral diversity is tolerated by central and effector memory CD8(+) T cells. 相似文献
154.
María Gabriela Cheluja Mariano Jos Scolari Trinidad María Coelho Mariano Guillermo Blake Mariano Martín Boccia Carlos María Baratti Gabriela Beatriz Acosta 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2007,146(4):499
Postnatal development changes in mechanisms of synaptosomal amino acid transport have been studied in rat cerebral cortex. Specific uptake of radiolabeled l-serine was examined and compared with that of radiolabeled GABA using synaptosomes-enriched fractions freshly prepared from cerebral cortex at different postnatal days from the birth to young adulthood. The preparations were incubated with 10 nM of [3H]l-serine and 10 nM of [3H]-GABA in either the presence or absence of NaCl, KCl or choline chloride, at 2 and 30 °C, for different periods up to 30 min. The uptake of [3H]l-serine was temperature dependent in synaptosomal fractions prepared from cerebral cortex of rats in postnatal days 5, 7, 13 and 21, but stronger dependence was observed in adult brain, irrespective of the presence of Na+, K+ or choline ions. At all postnatal ages studied, [3H]-GABA uptake showed a high activity in the presence of Na+ ions and at 30 °C. The values of Km were 90–489 μM in l-serine uptake. However, in the uptake of GABA the values of Km were 80–150 μM. The highest values of Vmax were obtained at 5 and 21 postnatal days for both transport systems. These results indicate that the uptake of l-serine and GABA are regulated differentially during postnatal development. 相似文献
155.
156.
Loiselle Bette A.; Ryder Thomas B.; Duraes Renata; Tori Wendy; Blake John G.; Parker Patricia G. 《Behavioral ecology》2007,18(2):287-291
In lek-mating systems, males aggregate at display arenas andfemales visit solely for the purpose of mating. This breedingsystem is characterized by high variance in male mating successwith one male often receiving most copulations. High reproductiveskew among males has led to question why males join leks whentheir chances of reproductive success are so low. Kin selectionhas been invoked as a mechanism to explain the evolution oflekking behavior, whereby nonreproducing but genetically relatedmales gain indirect inclusive-fitness benefits. Evidence forkin selection among lek-mating birds is, however, mixed. Here,we show that kin selection is unlikely to be an important explanationfor evolution of lekking behavior in manakins (Aves: Pipridae).We found that for 4 species chosen from several major cladeswithin Pipridae, males within leks were not significantly morerelated than expected from random assortment of males in thepopulation. This means that nonreproducing males do not gainindirect inclusive-fitness benefits by joining leks. This resultsuggests alternative mechanisms must be invoked to explain theevolution of lek-mating systems in manakins. 相似文献
157.
Recognition and Response to Native and Novel Predators in the Largespring mosquitofish,Gambusia geiseri
下载免费PDF全文
![点击此处可从《Ethology : formerly Zeitschrift fur Tierpsychologie》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Chelsea A. Blake Laura Alberici da Barbiano Jessica E. Guenther Caitlin R. Gabor 《Ethology : formerly Zeitschrift fur Tierpsychologie》2015,121(3):227-235
The introduction of predator species into new habitats is an increasingly common consequence of human activities, and the persistence of native prey species depends upon their response to these novel predators. In this study, we examined whether the Largespring mosquitofish, Gambusia geiseri exhibited antipredator behavior and/or an elevation of circulating stress hormones (cortisol) to visual and chemical cues from a native predator, a novel predator, or a non‐predatory control fish. Prey showed the most pronounced antipredator response to the native predator treatment, by moving away from the stimulus, while the prey showed no significant changes in their vertical or horizontal position in response to the novel or non‐predator treatments. We also found no significant difference in water‐borne cortisol release rates following any of the treatments. Our results suggest the prey did not recognize and exhibit antipredator behavior to the novel predator, and we infer that this predator species could be detrimental if it expands into the range of this prey species. Further, our study demonstrates prey may not respond to an invasive predator that is phylogenetically, behaviorally, and morphologically dissimilar from the prey species' native predators. 相似文献
158.
Jessica L. Woolnough Blake L. Atwood Keith E. Giles 《Molecular and cellular biology》2015,35(13):2278-2294
To further our understanding of the RNAi machinery within the human nucleus, we analyzed the chromatin and RNA binding of Argonaute 2 (AGO2) within human cancer cell lines. Our data indicated that AGO2 binds directly to nascent tRNA and 5S rRNA, and to the genomic loci from which these RNAs are transcribed, in a small RNA- and DICER-independent manner. AGO2 chromatin binding was not observed at non-TFIIIC-dependent RNA polymerase III (Pol III) genes or at extra-TFIIIC (ETC) sites, indicating that the interaction is specific for TFIIIC-dependent Pol III genes. A genome-wide analysis indicated that loss of AGO2 caused a global increase in mRNA expression level among genes that flank AGO2-bound tRNA genes. This effect was shown to be distinct from that of the disruption of DICER, DROSHA, or CTCF. We propose that AGO2 binding to tRNA genes has a novel and important regulatory role in human cells. 相似文献
159.
CRISPR-STAT: an easy and reliable PCR-based method to evaluate target-specific sgRNA activity 总被引:1,自引:0,他引:1
Blake Carrington Gaurav K. Varshney Shawn M. Burgess Raman Sood 《Nucleic acids research》2015,43(22):e157
CRISPR/Cas9 has emerged as a versatile genome-engineering tool that relies on a single guide RNA (sgRNA) and the Cas9 enzyme for genome editing. Simple, fast and economical methods to generate sgRNAs have made targeted mutagenesis routine in cultured cells, mice, zebrafish and other model systems. Pre-screening of sgRNAs for target efficacy is desirable both for successful mutagenesis and minimizing wasted animal husbandry on targets with poor activity. Here, we describe an easy, quick and cost-effective fluorescent polymerase chain reaction (PCR)-based method, CRISPR Somatic Tissue Activity Test (CRISPR-STAT), to determine target-specific efficiency of sgRNA. As a proof of principle, we validated our method using 28 sgRNAs with known and varied levels of germline transmission efficiency in zebrafish by analysis of their somatic activity in injected embryos. Our data revealed a strong positive correlation between the fluorescent PCR profiles of the injected embryos and the germline transmission efficiency. Furthermore, the assay was sensitive enough to evaluate multiplex gene targeting. This method is easy to implement by laboratories with access to a capillary sequencer. Although we validated the method using CRISPR/Cas9 and zebrafish, it can be applied to other model systems and other genome targeting nucleases. 相似文献
160.