全文获取类型
收费全文 | 2154篇 |
免费 | 131篇 |
国内免费 | 2篇 |
出版年
2023年 | 10篇 |
2022年 | 16篇 |
2021年 | 56篇 |
2020年 | 22篇 |
2019年 | 33篇 |
2018年 | 39篇 |
2017年 | 43篇 |
2016年 | 70篇 |
2015年 | 93篇 |
2014年 | 126篇 |
2013年 | 136篇 |
2012年 | 190篇 |
2011年 | 156篇 |
2010年 | 129篇 |
2009年 | 119篇 |
2008年 | 131篇 |
2007年 | 121篇 |
2006年 | 106篇 |
2005年 | 101篇 |
2004年 | 105篇 |
2003年 | 103篇 |
2002年 | 77篇 |
2001年 | 31篇 |
2000年 | 18篇 |
1999年 | 17篇 |
1998年 | 23篇 |
1997年 | 18篇 |
1996年 | 16篇 |
1995年 | 18篇 |
1994年 | 11篇 |
1993年 | 11篇 |
1992年 | 9篇 |
1991年 | 7篇 |
1990年 | 8篇 |
1989年 | 8篇 |
1988年 | 10篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 13篇 |
1984年 | 12篇 |
1983年 | 6篇 |
1982年 | 4篇 |
1980年 | 5篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1974年 | 6篇 |
1969年 | 2篇 |
1968年 | 2篇 |
1948年 | 3篇 |
1947年 | 2篇 |
排序方式: 共有2287条查询结果,搜索用时 15 毫秒
171.
Edito Fabrizio Nicola Vanacore Marcella Valente Alfonso Rubino Giuseppe Meco 《BMC neurology》2007,7(1):24
Background
Occupational and chronic exposure to solvents and metals is considered a possible risk factor for Parkinson's disease and essential tremor. While manufacturing dental prostheses, dental technicians are exposed to numerous chemicals that contain toxins known to affect the central nervous system, such as solvents (which contain n-hexane in particular) and metals (which contain mercury, iron, chromium, cobalt and nickel). 相似文献172.
Laccaria bicolor aquaporin LbAQP1 is required for Hartig net development in trembling aspen (Populus tremuloides)
下载免费PDF全文
![点击此处可从《Plant, cell & environment》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Alfonso Navarro‐RóDenas Hao Xu Minna Kemppainen Alejandro G. Pardo Janusz J. Zwiazek 《Plant, cell & environment》2015,38(11):2475-2486
The development of ectomycorrhizal associations is crucial for growth of many forest trees. However, the signals that are exchanged between the fungus and the host plant during the colonization process are still poorly understood. In this study, we have identified the relationship between expression patterns of Laccaria bicolor aquaporin LbAQP1 and the development of ectomycorrhizal structures in trembling aspen (Populus tremuloides) seedlings. The peak expression of LbAQP1 was 700‐fold higher in the hyphae within the root than in the free‐living mycelium after 24 h of direct interaction with the roots. Moreover, in LbAQP1 knock‐down strains, a non‐mycorrhizal phenotype was developed without the Hartig net and the expression of the mycorrhizal effector protein MiSSP7 quickly declined after an initial peak on day 5 of interaction of the fungal hyphae with the roots. The increase in the expression of LbAQP1 required a direct contact of the fungus with the root and it modulated the expression of MiSSP7. We have also determined that LbAQP1 facilitated NO, H2O2 and CO2 transport when heterologously expressed in yeast. The report demonstrates that the L. bicolor aquaporin LbAQP1 acts as a molecular signalling channel, which is fundamental for the development of Hartig net in root tips of P. tremuloides. 相似文献
173.
Margaux Bouzin Laura Sironi Giuseppe Chirico Laura D’Alfonso Donato Inverso Piersandro Pallavicini Maddalena Collini 《Biophysical journal》2015,109(11):2246-2258
Anisotropic metallic nanoparticles have been devised as powerful potential tools for in vivo imaging, photothermal therapy, and drug delivery thanks to plasmon-enhanced absorption and scattering cross sections, ease in synthesis and functionalization, and controlled cytotoxicity. The rational design of all these applications requires the characterization of the nanoparticles intracellular trafficking pathways. In this work, we exploit live-cell time-lapse confocal reflectance microscopy and image correlation in both direct and reciprocal space to investigate the intracellular transport of branched gold nanostars (GNSs). Different transport mechanisms, spanning from pure Brownian diffusion to (sub-)ballistic superdiffusion, are revealed by temporal and spatio-temporal image correlation spectroscopy on the tens-of-seconds timescale. According to these findings, combined with numerical simulations and with a Bayesian (hidden Markov model-based) analysis of single particle tracking data, we ascribe the superdiffusive, subballistic behavior characterizing the GNSs dynamics to a two-state switching between Brownian diffusion in the cytoplasm and molecular motor-mediated active transport. For the investigation of intermittent-type transport phenomena, we derive an analytical theoretical framework for Fourier-space image correlation spectroscopy (kICS). At first, we evaluate the influence of all the dynamic and kinetic parameters (the diffusion coefficient, the drift velocity, and the transition rates between the diffusive and the active transport regimes) on simulated kICS correlation functions. Then we outline a protocol for data analysis and employ it to derive whole-cell maps for each parameter underlying the GNSs intracellular dynamics. Capable of identifying even simpler transport phenomena, whether purely diffusive or ballistic, our intermittent kICS approach allows an exhaustive investigation of the dynamics of GNSs and biological macromolecules. 相似文献
174.
Estefanía Salvarelli Marcin Krupka Germán Rivas Jesus Mingorance Paulino Gómez-Puertas Carlos Alfonso Ana Isabel Rico 《The Journal of biological chemistry》2015,290(41):25081-25089
The cell division protein FtsZ assembles in vitro by a mechanism of cooperative association dependent on GTP, monovalent cations, and Mg2+. We have analyzed the GTPase activity and assembly dynamics of Streptococcus pneumoniae FtsZ (SpnFtsZ). SpnFtsZ assembled in an apparently cooperative process, with a higher critical concentration than values reported for other FtsZ proteins. It sedimented in the presence of GTP as a high molecular mass polymer with a well defined size and tended to form double-stranded filaments in electron microscope preparations. GTPase activity depended on K+ and Mg2+ and was inhibited by Na+. GTP hydrolysis exhibited a delay that included a lag phase followed by a GTP hydrolysis activation step, until reaction reached the GTPase rate. The lag phase was not found in polymer assembly, suggesting a transition from an initial non-GTP-hydrolyzing polymer that switches to a GTP-hydrolyzing polymer, supporting models that explain FtsZ polymer cooperativity. 相似文献
175.
176.
David S. Gokhin Roberta B. Nowak Joseph A. Khoory Alfonso de la Piedra Ionita C. Ghiran Velia M. Fowler 《Molecular biology of the cell》2015,26(9):1699-1710
Short, uniform-length actin filaments function as structural nodes in the spectrin-actin membrane skeleton to optimize the biomechanical properties of red blood cells (RBCs). Despite the widespread assumption that RBC actin filaments are not dynamic (i.e., do not exchange subunits with G-actin in the cytosol), this assumption has never been rigorously tested. Here we show that a subpopulation of human RBC actin filaments is indeed dynamic, based on rhodamine-actin incorporation into filaments in resealed ghosts and fluorescence recovery after photobleaching (FRAP) analysis of actin filament mobility in intact RBCs (∼25–30% of total filaments). Cytochalasin-D inhibition of barbed-end exchange reduces rhodamine-actin incorporation and partially attenuates FRAP recovery, indicating functional interaction between actin subunit turnover at the single-filament level and mobility at the membrane-skeleton level. Moreover, perturbation of RBC actin filament assembly/disassembly with latrunculin-A or jasplakinolide induces an approximately twofold increase or ∼60% decrease, respectively, in soluble actin, resulting in altered membrane deformability, as determined by alterations in RBC transit time in a microfluidic channel assay, as well as by abnormalities in spontaneous membrane oscillations (flickering). These experiments identify a heretofore-unrecognized but functionally important subpopulation of RBC actin filaments, whose properties and architecture directly control the biomechanical properties of the RBC membrane. 相似文献
177.
Julián Alexander Mendivil Nieto Ranulfo González Obando Alfonso Neri García Aldrete 《ZooKeys》2015,(503):45-54
Two new species of Edmockfordia García Aldrete, from Valle del Cauca, Colombia, and the female of Edmockfordia
chiquibulensis García Aldrete, are described and illustrated. A key to the species of Edmockfordia is included; the genus was previously known only from Belize. The genus is re-diagnosed to include female characters. The distribution of the genus is considerably widened, from Belize to northeastern South America. 相似文献
178.
Julie Earl Daniel Rico Enrique Carrillo-de-Santa-Pau Benjamín Rodríguez-Santiago Marinela Méndez-Pertuz Herbert Auer Gonzalo Gómez Herbert Barton Grossman David G Pisano Wolfgang A Schulz Luis A Pérez-Jurado Alfredo Carrato Dan Theodorescu Stephen Chanock Alfonso Valencia Francisco X Real 《BMC genomics》2015,16(1)
Background
Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.Results
Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.Conclusions
Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1450-3) contains supplementary material, which is available to authorized users. 相似文献179.
Omar EstradaJuan Manuel González-Guzmán Margarita Salazar-BookamanAna Z. Fernández Alfonso CardozoClaudia Alvarado-Castillo 《Phytomedicine》2011,18(6):464-469
Pomolic acid has recently shown hypotensive effect in rats. The purpose of this investigation was to determine the vascular effects of this triterpenoid and to examine its mode of action. Functional experiments in rat aortic rings precontracted with norepinephrine were performed to evaluate the vasorelaxant effect of pomolic acid. This triterpenoid induced a vasorelaxation (IC50 = 2.45 μM) in a concentration- and endothelium-dependent manner and showed no effect on contractions evoked by KCl (25 mM). Pre-treatment of aortic rings with l-NAME (100 μM), methylene blue (100 μM) or glibenclamide (10 μM), totally prevented the vasorelaxation induced by pomolic acid, while indomethacin (10 μM) had no effect on this response. Additionally, pomolic acid relaxation was unaffected under the muscarinic- and β-adrenergic-receptor blocked ensured for atropine and propanolol respectively (10 μM each). In contrast, the vasorelaxant effect of pomolic acid was abolished under the purinergic-receptor blocked ensured for suramin (10 μM). Finally, apyrase (0.8 U/ml) an enzyme which hydrolyses ATP and ADP did not affect pomolic acid relaxation. In summary, pomolic acid has a potent endothelium-dependent vasorelaxant effect, possibly acting through the direct activation of endothelial purinergic receptors via NO-cGMP signaling pathway, which could be part of the mechanism underlying its hypotensive effect. 相似文献
180.
Stem and progenitor cells are populations of cells that retain the capacity to populate specific lineages and to transit this capacity through cell division. However, attempts to define markers for stem cells have met with limited success. Here we consider whether this limited success reflects an intrinsic requirement for heterogeneity with stem cell populations. We focus on Embryonic Stem (ES) cells, in vitro derived cell lines from the early embryo that are considered both pluripotent (able to generate all the lineages of the future embryo) and indefinitely self renewing. We examine the relevance of recently reported heterogeneities in ES cells and whether these heterogeneities themselves are inherent requirements of functional potency and self renewal. 相似文献