全文获取类型
收费全文 | 265篇 |
免费 | 29篇 |
出版年
2023年 | 2篇 |
2022年 | 3篇 |
2021年 | 8篇 |
2020年 | 8篇 |
2019年 | 3篇 |
2018年 | 6篇 |
2017年 | 5篇 |
2016年 | 9篇 |
2015年 | 15篇 |
2014年 | 19篇 |
2013年 | 27篇 |
2012年 | 29篇 |
2011年 | 21篇 |
2010年 | 18篇 |
2009年 | 17篇 |
2008年 | 20篇 |
2007年 | 17篇 |
2006年 | 15篇 |
2005年 | 16篇 |
2004年 | 7篇 |
2003年 | 5篇 |
2002年 | 7篇 |
2001年 | 2篇 |
2000年 | 2篇 |
1999年 | 2篇 |
1998年 | 1篇 |
1997年 | 1篇 |
1994年 | 1篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1983年 | 1篇 |
1982年 | 2篇 |
1981年 | 1篇 |
1976年 | 1篇 |
1972年 | 1篇 |
排序方式: 共有294条查询结果,搜索用时 46 毫秒
41.
Latisha D. Heinlen Micah T. McClain Lauren L. Ritterhouse Benjamin F. Bruner Colin C. Edgerton Michael P. Keith Judith A. James John B. Harley 《PloS one》2010,5(3)
Systemic lupus erythematosus (SLE) is a clinically heterogeneous, humoral autoimmune disorder. The unifying feature among SLE patients is the production of large quantities of autoantibodies. Serum samples from 129 patients collected before the onset of SLE and while in the United States military were evaluated for early pre-clinical serologic events. The first available positive serum sample frequently already contained multiple autoantibody specificities (65%). However, in 34 SLE patients the earliest pre-clinical serum sample positive for any detectable common autoantibody bound only a single autoantigen, most commonly 60 kD Ro (29%), nRNP A (24%), anti-phospholipids (18%) or rheumatoid factor (15%). We identified several recurrent patterns of autoantibody onset using these pre-diagnostic samples. In the serum samples available, anti-nRNP A appeared before or simultaneously with anti-nRNP 70 K in 96% of the patients who had both autoantibodies at diagnosis. Anti-60 kD Ro antibodies appeared before or simultaneously with anti-La (98%) or anti-52 kD Ro (95%). The autoantibody response in SLE patients begins simply, often binding a single specific autoantigen years before disease onset, followed by epitope spreading to additional autoantigenic specificities that are accrued in recurring patterns. 相似文献
42.
Nikitin PA Yan CM Forte E Bocedi A Tourigny JP White RE Allday MJ Patel A Dave SS Kim W Hu K Guo J Tainter D Rusyn E Luftig MA 《Cell host & microbe》2010,8(6):510-522
Epstein-Barr virus (EBV), an oncogenic herpesvirus that causes human malignancies, infects and immortalizes primary human B cells in?vitro into indefinitely proliferating lymphoblastoid cell lines, which represent a model for EBV-induced tumorigenesis. The immortalization efficiency is very low, suggesting that an innate tumor suppressor mechanism is operative. We identify the DNA damage response (DDR) as?a major component of the underlying tumor suppressor mechanism. EBV-induced DDR activation was not due to lytic viral replication, nor did the DDR marks colocalize with latent episomes. Rather, a transient period of EBV-induced hyperproliferation correlated with DDR activation. Inhibition of the DDR kinases ATM and Chk2 markedly increased transformation efficiency of primary B cells. Further, the viral latent oncoprotein EBNA3C was required to attenuate the EBV-induced DDR. We propose that heightened oncogenic activity in early cell divisions activates a growth-suppressive DDR that is attenuated by viral latency products to induce cell immortalization. 相似文献
43.
Cédric Berney Andreea Ciuprina Sara Bender Juliet Brodie Virginia Edgcomb Eunsoo Kim Jeena Rajan Laura Wegener Parfrey Sina Adl Stéphane Audic David Bass David A. Caron Guy Cochrane Lucas Czech Micah Dunthorn Stefan Geisen Frank Oliver Glöckner Frédéric Mahé Christian Quast Jonathan Z. Kaye Alastair G. B. Simpson Alexandros Stamatakis Javier del Campo Pelin Yilmaz Colomban de Vargas 《The Journal of eukaryotic microbiology》2017,64(3):407-411
Universal taxonomic frameworks have been critical tools to structure the fields of botany, zoology, mycology, and bacteriology as well as their large research communities. Animals, plants, and fungi have relatively solid, stable morpho‐taxonomies built over the last three centuries, while bacteria have been classified for the last three decades under a coherent molecular taxonomic framework. By contrast, no such common language exists for microbial eukaryotes, even though environmental ‘‐omics’ surveys suggest that protists make up most of the organismal and genetic complexity of our planet's ecosystems! With the current deluge of eukaryotic meta‐omics data, we urgently need to build up a universal eukaryotic taxonomy bridging the protist ‐omics age to the fragile, centuries‐old body of classical knowledge that has effectively linked protist taxa to morphological, physiological, and ecological information. UniEuk is an open, inclusive, community‐based and expert‐driven international initiative to build a flexible, adaptive universal taxonomic framework for eukaryotes. It unites three complementary modules, EukRef, EukBank, and EukMap, which use phylogenetic markers, environmental metabarcoding surveys, and expert knowledge to inform the taxonomic framework. The UniEuk taxonomy is directly implemented in the European Nucleotide Archive at EMBL‐EBI, ensuring its broad use and long‐term preservation as a reference taxonomy for eukaryotes. 相似文献
44.
Proper functioning of the innate immune response depends on migration of circulating neutrophils into tissues at sites of infection and inflammation. Migration of highly motile, amoeboid cells such as neutrophils has significant physiological relevance, yet the traction forces that drive neutrophil motion in response to chemical cues are not well characterized. To better understand the relationship between chemotactic signals and the organization of forces in motile neutrophils, force measurements were made on hydrogel surfaces under well-defined chemotactic gradients created with a microfluidic device. Two parameters, the mean chemoattractant concentration (CM) and the gradient magnitude (Δc/Δx) were varied. Cells experiencing a large gradient with CM near the chemotactic receptor KD displayed strong punctate centers of uropodial contractile force and strong directional motion on stiff (12 kPa) surfaces. Under conditions of ideal chemotaxis—cells in strong gradients with mean chemoattractant near the receptor KD and on stiffer substrates—there is a correlation between the magnitude of force generation and directional motion as measured by the chemotactic index. However, on soft materials or under weaker chemotactic conditions, directional motion is uncorrelated with the magnitude of traction force. Inhibition of either β2 integrins or Rho-associated kinase, a kinase downstream from RhoA, greatly reduced rearward traction forces and directional motion, although some vestigial lamellipodium-driven motility remained. In summary, neutrophils display a diverse repertoire of methods for organizing their internal machinery to generate directional motion. 相似文献
45.
46.
Megan K. Watson Adam W. Stern Amber L. Labelle Stephen Joslyn Timothy M. Fan Katie Leister Micah Kohles Kemba Marshall Mark A. Mitchell 《PloS one》2014,9(12)
Vitamin D is an important hormone in vertebrates. Most animals acquire this hormone through their diet, secondary to exposure to ultraviolet B (UVB) radiation, or a combination thereof. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on guinea pigs (Cavia porcellus) and to evaluate the long-term safety of artificial UVB light supplementation over the course of six months. Twelve juvenile acromelanic Hartley guinea pigs were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received only ambient fluorescent light for 12 hours daily. Animals in both groups were offered the same diet and housed under the same conditions. Blood samples were collected every three weeks to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D3 (25-OHD3) levels. Serial ophthalmologic examinations, computed tomography scans, and dual energy x-ray absorptiometry scans were performed during the course of the study. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD3 concentrations differed significantly in the guinea pigs (p<0.0001) between the UVB supplementation group (101.49±21.81 nmol/L) and the control group (36.33±24.42 nmol/L). An increased corneal thickness in both eyes was also found in the UVB supplementation compared to the control group (right eye [OD]: p<0.0001; left eye [OS]: p<0.0001). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing guinea pigs to UVB radiation long term significantly increased their circulating serum 25-OHD3 levels, and that this increase was sustainable over time. Providing guinea pigs exposure to UVB may be an important husbandry consideration that is not currently recommended. 相似文献
47.
Extreme weather conditions correspond with localised vegetation death at Cradle Mountain,Tasmania
下载免费PDF全文
![点击此处可从《Ecological Management & Restoration》网站下载免费的PDF全文](/ch/ext_images/free.gif)
A chance observation of a drought‐related plant mortality event in early 2014 in a normally wet and cool alpine area was matched with local weather data providing a unique insight into this event. The observed plant death was largely indiscriminate in areas that were topographically predisposed to being susceptible to drought. The weather conditions surrounding this event included 5 weeks with very little rain, an extreme heatwave and subsequent brief periods where warm temperatures and dry air combined to produce highly evaporative conditions. Extreme weather conditions such as this are expected to occur with increasing frequency as a result of climate change. Observing and reporting on real‐world examples of how extreme weather events affect native vegetation is integral to improved climate change risk assessment and to inform future management actions. 相似文献
48.
Synaptic function is critical for proper cognition, and synaptopathologies have
been implicated in diverse neuropsychiatric disorders. STriatal-Enriched protein
tyrosine Phosphatase (STEP) is a brain-enriched tyrosine phosphatase that
normally opposes synaptic strengthening by dephosphorylating key neuronal
signaling molecules. STEP targets include N-methyl D-aspartate receptors
(NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors
(AMPARs), as well as extracellular signal-regulated kinase (ERK) and the
tyrosine kinase Fyn. STEP-mediated dephosphorylation promotes the
internalization of NMDARs and AMPARs and the inactivation of ERK and Fyn.Regulation of STEP is complex, and recent work has implicated STEP dysregulation
in the pathophysiology of several neuropsychiatric disorders. Both high levels
and low levels of STEP are found in a diverse group of illnesses. This review
focuses on the role of STEP in three disorders in which STEP levels are
elevated: Alzheimer’s disease, fragile X syndrome, and schizophrenia. The
presence of elevated STEP in all three of these disorders raises the intriguing
possibility that cognitive deficits resulting from diverse etiologies may share
a common molecular pathway. 相似文献
49.
Consistent patterns of high alpha and low beta diversity in tropical parasitic and free‐living protists
下载免费PDF全文
![点击此处可从《Molecular ecology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Guillaume Lentendu Frédéric Mahé David Bass Sonja Rueckert Thorsten Stoeck Micah Dunthorn 《Molecular ecology》2018,27(13):2846-2857
Tropical animals and plants are known to have high alpha diversity within forests, but low beta diversity between forests. By contrast, it is unknown whether microbes inhabiting the same ecosystems exhibit similar biogeographic patterns. To evaluate the biogeographies of tropical protists, we used metabarcoding data of species sampled in the soils of three lowland Neotropical rainforests. Taxa–area and distance–decay relationships for three of the dominant protist taxa and their subtaxa were estimated at both the OTU and phylogenetic levels, with presence–absence and abundance‐based measures. These estimates were compared to null models. High local alpha and low regional beta diversity patterns were consistently found for both the parasitic Apicomplexa and the largely free‐living Cercozoa and Ciliophora. Similar to animals and plants, the protists showed spatial structures between forests at the OTU and phylogenetic levels, and only at the phylogenetic level within forests. These results suggest that the biogeographies of macro‐ and micro‐organismal eukaryotes in lowland Neotropical rainforests are partially structured by the same general processes. However, and unlike the animals and plants, the protist OTUs did not exhibit spatial structures within forests, which hinders our ability to estimate the local and regional diversity of protists in tropical forests. 相似文献
50.