全文获取类型
收费全文 | 129篇 |
免费 | 8篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 5篇 |
2019年 | 5篇 |
2017年 | 3篇 |
2016年 | 4篇 |
2015年 | 7篇 |
2014年 | 8篇 |
2013年 | 7篇 |
2012年 | 8篇 |
2011年 | 11篇 |
2010年 | 8篇 |
2009年 | 5篇 |
2008年 | 8篇 |
2007年 | 6篇 |
2006年 | 6篇 |
2005年 | 7篇 |
2004年 | 2篇 |
2003年 | 4篇 |
2002年 | 5篇 |
2001年 | 1篇 |
2000年 | 2篇 |
1998年 | 1篇 |
1993年 | 1篇 |
1992年 | 2篇 |
1989年 | 2篇 |
1987年 | 2篇 |
1975年 | 1篇 |
1973年 | 4篇 |
1971年 | 2篇 |
1970年 | 2篇 |
1969年 | 1篇 |
1965年 | 2篇 |
1964年 | 2篇 |
排序方式: 共有137条查询结果,搜索用时 15 毫秒
1.
Francesca Zito Demian Koop Maria Byrne Valeria Matranga 《Development, growth & differentiation》2015,57(7):507-514
Carbonic anhydrases (CAs) are a family of widely distributed metalloenzymes, involved in diverse physiological processes. These enzymes catalyse the reversible conversion of carbon dioxide to protons and bicarbonate. At least 19 genes encoding for CAs have been identified in the sea urchin genome, with one of these localized to the skeletogenic mesoderm (primary mesenchyme cells, PMCs). We investigated the effects of a specific inhibitor of CA, acetazolamide (AZ), on development of two sea urchin species with contrasting investment in skeleton production, Paracentrotus lividus and Heliocidaris tuberculata, to determine the role of CA on PMC differentiation, skeletogenesis and on non‐skeletogenic mesodermal (NSM) cells. Embryos were cultured in the presence of AZ from the blastula stage prior to skeleton formation and development to the larval stage was monitored. At the dose of 8 mmol/L AZ, 98% and 90% of P. lividus and H. tuberculata embryos lacked skeleton, respectively. Nevertheless, an almost normal PMC differentiation was indicated by the expression of msp130, a PMC‐specific marker. Strikingly, the AZ‐treated embryos also lacked the echinochrome pigment produced by the pigment cells, a subpopulation of NSM cells with immune activities within the larva. Conversely, all ectoderm and endoderm derivatives and other subpopulations of mesoderm developed normally. The inhibitory effects of AZ were completely reversed after removal of the inhibitor from the medium. Our data, together with new information concerning the involvement of CA on skeleton formation, provide evidence for the first time of a possible role of the CAs in larval immune pigment cells. 相似文献
2.
The nervous system is ectodermal in origin. All nerve ganglia arise separately by proliferation and later delamination from the ectoderm, not by invagination. They become secondarily connected to one another by commissures and connectives developing as extensions from the peripheral layer of ganglionic nerve cells. Rudiments of the cerebral, pedal, pleural and intestinal (parietal) ganglia arise almost simultaneously at a relatively early stage (Stage V). The cerebral ganglia develop from the ectoderm of the head plates. Rudiments of the pedal and pleural ganglia are separate at their inception. They later fuse (Stage VI) to form a pleuro-pedal ganglionic mass on each side. The 2 intestinal ganglia are symmetrical at the beginning, but they soon lose their symmetry as a result of torsion. The right ganglion crosses to the left over the gut and persists as the supraintestinal ganglion. The left or subintestinal ganglion shifts to the right and forward, and fuses with the right pleural ganglion (Stage VIII), thus obscuring the chiastoneury. The paired buccal and single visceral (abdominal) ganglia start differentiating in Stage VII. The former develop from the ectodermal wall of the stomodaeum, while the visceral ganglion delaminates from the right wall of the visceral sac, then shifts to the left during torsion. The statocysts develop early (Stage V) from 2 ectodermal invaginations on either side of the rudimentary foot. They later separate from the overlying ectoderm and statoconi appear in their lumina. Contrary to earlier reports on related ampullariids, the osphradium proved to be ontogenetically older than the mantle and mantle cavity. It starts differentiating as a thickened ectodermal plate in the right wall of the visceral sac (Stage V). During torsion, it becomes engulfed in the mantle cavity and shifts to the left side, then is carried forward as the mantlegrow. The eyes develop late (Stage IX) as ectodermal invaginations which rapidly separate from the ectoderm to form closed vesicles. Their cells start differentiating before hatching to form the retina, in which pigment is deposited, and the inner cornea. The lens is secreted in the lumen of the eye and grows by addition of concentric layers of secretion. 相似文献
3.
The SR family proteins and SR-related polypeptides are important regulators of pre-mRNA splicing. A novel SR-related protein of an apparent molecular mass of 53 kDa was isolated in a gene trap screen that identifies proteins which localize to the nuclear speckles. This novel protein possesses an arginine- and serine-rich domain and was termed SRrp53 (for SR-related protein of 53 kDa). In support for a role of this novel RS-containing protein in pre-mRNA splicing, we identified the mouse ortholog of the Saccharomyces cerevisiae U1 snRNP-specific protein Luc7p and the U2AF65-related factor HCC1 as interacting proteins. In addition, SRrp53 is able to interact with some members of the SR family of proteins and with U2AF35 in a yeast two-hybrid system and in cell extracts. We show that in HeLa nuclear extracts immunodepleted of SRrp53, the second step of pre-mRNA splicing is blocked, and recombinant SRrp53 is able to restore splicing activity. SRrp53 also regulates alternative splicing in a concentration-dependent manner. Taken together, these results suggest that SRrp53 is a novel SR-related protein that has a role both in constitutive and in alternative splicing. 相似文献
4.
Inbal Gamliel Yehezkel Buba Tamar Guy-Haim Tal Garval Demian Willette Gil Rilov Jonathan Belmaker 《Ecography》2020,43(7):1090-1106
Species distribution models (SDMs) correlate species occurrences with environmental predictors, and can be used to forecast distributions under future climates. SDMs have been criticized for not explicitly including the physiological processes underlying the species response to the environment. Recently, new methods have been suggested to combine SDMs with physiological estimates of performance (physiology-SDMs). In this study, we compare SDM and physiology-SDM predictions for select marine species in the Mediterranean Sea, a region subjected to exceptionally rapid climate change. We focused on six species and created physiology-SDMs that incorporate physiological thermal performance curves from experimental data with species occurrence records. We then contrasted projections of SDMs and physiology-SDMs under future climate (year 2100) for the entire Mediterranean Sea, and particularly the ‘warm’ trailing edge in the Levant region. Across the Mediterranean, we found cross-validation model performance to be similar for regular SDMs and physiology-SDMs. However, we also show that for around half the species the physiology-SDMs substantially outperform regular SDM in the warm Levant. Moreover, for all species the uncertainty associated with the coefficients estimated from the physiology-SDMs were much lower than in the regular SDMs. Under future climate, we find that both SDMs and physiology-SDMs showed similar patterns, with species predicted to shift their distribution north-west in accordance with warming sea temperatures. However, for the physiology-SDMs predicted distributional changes are more moderate than those predicted by regular SDMs. We conclude, that while physiology-SDM predictions generally agree with the regular SDMs, incorporation of the physiological data led to less extreme range shift forecasts. The results suggest that climate-induced range shifts may be less drastic than previously predicted, and thus most species are unlikely to completely disappear with warming climate. Taken together, the findings emphasize that physiological experimental data can provide valuable supplemental information to predict range shifts of marine species. 相似文献
5.
Feldheim Kevin A. Jabado Rima W. Chapman Demian D. Cardeñosa Diego Maddox J. Dylan 《Molecular biology reports》2020,47(4):2669-2675
Molecular Biology Reports - Microsatellites are useful in studies of population genetics, sibship, and parentage. Here, we screened for microsatellites from multiple elasmobranch genomic libraries... 相似文献
6.
Ludovic Reveiz Stephanie Sangalang Demian Glujovsky Carlos E. Pinzon Claudia Asenjo Lobos Marcela Cortes Martin Ca?ón Ariel Bardach Xavier Bonfill 《PloS one》2013,8(2)
Introduction
Few studies have assessed the nature and quality of randomized controlled trials (RCTs) in Latin America and the Caribbean (LAC).Methods and Findings
The aims of this systematic review are to evaluate the characteristics (including the risk of bias assessment) of RCT conducted in LAC according to funding source. A review of RCTs published in 2010 in which the author''s affiliation was from LAC was performed in PubMed and LILACS. Two reviewers independently extracted data and assessed the risk of bias. The primary outcomes were risk of bias assessment and funding source. A total of 1,695 references were found in PubMed and LILACS databases, of which 526 were RCTs (N = 73.513 participants). English was the dominant publication language (93%) and most of the RCTs were published in non-LAC journals (84.2%). Only five of the 19 identified countries accounted for nearly 95% of all RCTs conducted in the region (Brazil 70.9%, Mexico 10.1%, Argentina 5.9%, Colombia 3.8%, and Chile 3.4%). Few RCTs covered priority areas related with Millennium Development Goals like maternal health (6.7%) or high priority infectious diseases (3.8%). Regarding children, 3.6% and 0.4% RCT evaluated nutrition and diarrhea interventions respectively but none pneumonia. As a comparison, aesthetic and sport related interventions account for 4.6% of all trials. A random sample of RCTs (n = 358) was assessed for funding source: exclusively public (33.8%); private (e.g. pharmaceutical company) (15.3%); other (e.g. mixed, NGO) (15.1%); no funding (35.8%). Overall assessments for risk of bias showed no statistically significant differences between RCTs and type of funding source. Statistically significant differences favoring private and others type of funding was found when assessing trial registration and conflict of interest reporting.Conclusion
Findings of this study could be used to provide more direction for future research to facilitate innovation, improve health outcomes or address priority health problems. 相似文献7.
Lucy A. Howey Emily R. Tolentino Yannis P. Papastamatiou Edward J. Brooks Debra L. Abercrombie Yuuki Y. Watanabe Sean Williams Annabelle Brooks Demian D. Chapman Lance K.B. Jordan 《Ecology and evolution》2016,6(15):5290-5304
Comprehension of ecological processes in marine animals requires information regarding dynamic vertical habitat use. While many pelagic predators primarily associate with epipelagic waters, some species routinely dive beyond the deep scattering layer. Actuation for exploiting these aphotic habitats remains largely unknown. Recent telemetry data from oceanic whitetip sharks (Carcharhinus longimanus) in the Atlantic show a strong association with warm waters (>20°C) less than 200 m. Yet, individuals regularly exhibit excursions into the meso‐ and bathypelagic zone. In order to examine deep‐diving behavior in oceanic whitetip sharks, we physically recovered 16 pop‐up satellite archival tags and analyzed the high‐resolution depth and temperature data. Diving behavior was evaluated in the context of plausible functional behavior hypotheses including interactive behaviors, energy conservation, thermoregulation, navigation, and foraging. Mesopelagic excursions (n = 610) occurred throughout the entire migratory circuit in all individuals, with no indication of site specificity. Six depth‐versus‐time descent and ascent profiles were identified. Descent profile shapes showed little association with examined environmental variables. Contrastingly, ascent profile shapes were related to environmental factors and appear to represent unique behavioral responses to abiotic conditions present at the dive apex. However, environmental conditions may not be the sole factors influencing ascents, as ascent mode may be linked to intentional behaviors. While dive functionality remains unconfirmed, our study suggests that mesopelagic excursions relate to active foraging behavior or navigation. Dive timing, prey constituents, and dive shape support foraging as the most viable hypothesis for mesopelagic excursions, indicating that the oceanic whitetip shark may regularly survey extreme environments (deep depths, low temperatures) as a foraging strategy. At the apex of these deep‐water excursions, sharks exhibit a variable behavioral response, perhaps, indicating the presence or absence of prey. 相似文献
8.
Siranush Babakhanova Erica E. Jung Kazuhiko Namikawa Hanbin Zhang Yangdong Wang Oksana M. Subach Dmitry A. Korzhenevskiy Tatiana V. Rakitina Xian Xiao Wenjing Wang Jing Shi Mikhail Drobizhev Demian Park Lea Eisenhard Hongyun Tang Reinhard W. Kster Fedor V. Subach Edward S. Boyden Kiryl D. Piatkevich 《Protein science : a publication of the Protein Society》2022,31(3):728
In vivo imaging of model organisms is heavily reliant on fluorescent proteins with high intracellular brightness. Here we describe a practical method for rapid optimization of fluorescent proteins via directed molecular evolution in cultured mammalian cells. Using this method, we were able to perform screening of large gene libraries containing up to 2 × 107 independent random genes of fluorescent proteins expressed in HEK cells, completing one iteration of directed evolution in a course of 8 days. We employed this approach to develop a set of green and near‐infrared fluorescent proteins with enhanced intracellular brightness. The developed near‐infrared fluorescent proteins demonstrated high performance for fluorescent labeling of neurons in culture and in vivo in model organisms such as Caenorhabditis elegans, Drosophila, zebrafish, and mice. Spectral properties of the optimized near‐infrared fluorescent proteins enabled crosstalk‐free multicolor imaging in combination with common green and red fluorescent proteins, as well as dual‐color near‐infrared fluorescence imaging. The described method has a great potential to be adopted by protein engineers due to its simplicity and practicality. We also believe that the new enhanced fluorescent proteins will find wide application for in vivo multicolor imaging of small model organisms. 相似文献
9.
Paris D Townsend KP Obregon DF Humphrey J Mullan M 《Prostaglandins & other lipid mediators》2002,70(1-2):1-12
It has recently been shown that the level of soluble beta-amyloid (Abeta) peptides correlates well with the severity of synaptic loss and the density of neurofibrillary tangles observed in Alzheimer's disease (AD) brain. However, the biological activity of soluble forms of Abeta peptides in the brain remains to be determined. We have investigated ex vivo the effect of freshly solubilized Abeta1-40 peptides (fsAbeta) on prostaglandin E2 (PGE2) production in rat brain slices. PGE2 levels increased rapidly following treatment with fsAbeta, an effect that was prevented by SB202190, a selective inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and by NS-398, which preferentially inhibits cyclooxygenase-2 (COX-2) compared to COX-1. In an attempt to determine the cellular systems of the brain responsible for prostaglandin production in response to fsAbeta, the effect of fsAbeta was tested on isolated brain microvessels, primary cultures of brain smooth muscle cells/pericytes and endothelial cells, and a human neuron-like cell line (IMR32). Our data show that fsAbeta ex vivo can stimulate prostaglandin accumulation in incubates of isolated rat brain microvessels. In addition, fsAbeta appears to cause a concentration-dependent enhancement of prostaglandin accumulation in primary cultures of brain microvessel-derived smooth muscle cells/pericytes but not of brain endothelial cells. Finally, fsAbeta also stimulated PGF2alpha accumulation in cultures of differentiated IMR32 cells, but to a lesser extent than in brain smooth muscle cell/pericyte cultures. Deposition of aggregated forms of Abeta in the brain has been thought to trigger an inflammatory response which accompanies the neuropathologic events of AD. Our data provide evidence that fsAbeta triggers a pro-inflammatory reaction in rat brain, and suggest that the cerebrovasculature may constitute an important source of pro-inflammatory eicosanoids. 相似文献
10.
Cazalla D Zhu J Manche L Huber E Krainer AR Cáceres JF 《Molecular and cellular biology》2002,22(19):6871-6882
Splicing factors of the SR protein family share a modular structure consisting of one or two RNA recognition motifs (RRMs) and a C-terminal RS domain rich in arginine and serine residues. The RS domain, which is extensively phosphorylated, promotes protein-protein interactions and directs subcellular localization and-in certain situations-nucleocytoplasmic shuttling of individual SR proteins. We analyzed mutant versions of human SF2/ASF in which the natural RS repeats were replaced by RD or RE repeats and compared the splicing and subcellular localization properties of these proteins to those of SF2/ASF lacking the entire RS domain or possessing a minimal RS domain consisting of 10 consecutive RS dipeptides (RS10). In vitro splicing of a pre-mRNA that requires an RS domain could take place when the mutant RD, RE, or RS10 domain replaced the natural domain. The RS10 version of SF2/ASF shuttled between the nucleus and the cytoplasm in the same manner as the wild-type protein, suggesting that a tract of consecutive RS dipeptides, in conjunction with the RRMs of SF2/ASF, is necessary and sufficient to direct nucleocytoplasmic shuttling. However, the SR protein SC35 has two long stretches of RS repeats, yet it is not a shuttling protein. We demonstrate the presence of a dominant nuclear retention signal in the RS domain of SC35. 相似文献