全文获取类型
收费全文 | 457篇 |
免费 | 51篇 |
国内免费 | 1篇 |
出版年
2022年 | 2篇 |
2021年 | 11篇 |
2020年 | 8篇 |
2019年 | 11篇 |
2018年 | 10篇 |
2017年 | 8篇 |
2016年 | 14篇 |
2015年 | 31篇 |
2014年 | 21篇 |
2013年 | 34篇 |
2012年 | 46篇 |
2011年 | 36篇 |
2010年 | 26篇 |
2009年 | 25篇 |
2008年 | 28篇 |
2007年 | 31篇 |
2006年 | 14篇 |
2005年 | 19篇 |
2004年 | 19篇 |
2003年 | 12篇 |
2002年 | 22篇 |
2001年 | 4篇 |
2000年 | 5篇 |
1999年 | 5篇 |
1998年 | 5篇 |
1997年 | 7篇 |
1995年 | 4篇 |
1994年 | 4篇 |
1993年 | 6篇 |
1992年 | 3篇 |
1991年 | 3篇 |
1989年 | 2篇 |
1988年 | 5篇 |
1986年 | 4篇 |
1985年 | 4篇 |
1984年 | 1篇 |
1982年 | 1篇 |
1981年 | 2篇 |
1980年 | 1篇 |
1978年 | 1篇 |
1976年 | 2篇 |
1975年 | 1篇 |
1973年 | 1篇 |
1972年 | 1篇 |
1970年 | 2篇 |
1967年 | 1篇 |
1964年 | 1篇 |
1957年 | 1篇 |
1955年 | 1篇 |
1916年 | 1篇 |
排序方式: 共有509条查询结果,搜索用时 31 毫秒
1.
Liakos Panagiotis; Bourmeyster Nicolas; Defaye Genevieve; Chambaz Edmond M.; Bottari Serge P. 《American journal of physiology. Cell physiology》1997,273(4):C1324
Angiotensin II(ANG II) has long been known for its pressor and growth-promotingeffects, which are both mediated by theAT1 receptor. By contrast, theAT2 receptor has recently beenreported to mediate inhibition of proliferation through as yetundefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks thecells in G1 phase. Consistent withthis, ANG II inhibits cyclin D1 expression and cyclinD1-associated kinase activity. Theantimitogenic effect of ANG II is partly mimicked by theAT2-selective agonist CGP-42112.It is also blocked partly and in an additive fashion by theAT1- andAT2-selective antagonists losartanand PD-123319, indicating the contribution of both receptor subtypes tothis response. AT1-dependentantiproliferation is selectively blocked by the cyclooxygenaseinhibitor indomethacin and restored by prostaglandin E2, whereasAT2-receptor-mediated inhibitionof growth is suppressed by the tyrosine phosphatase inhibitorsorthovanadate and bpV(pic). Both pathways are, however,pertussis toxin sensitive. We hypothesize that, in fasciculatacells, the AT1 receptor inhibitsbFGF-induced proliferation by stimulating prostaglandin synthesis,whereas the AT2 receptor mediatesits effect through a pathway that requires protein tyrosine phosphataseactivation. 相似文献
2.
The ability of an invasive plant to occupy new areas is often attributed to both morphological and physiological plasticities
that allow them to remain viable over a wide range of environmental conditions. Studies addressing the ecological requirements
of Microstegium vimineum often consider soil moisture or soil moisture along with other factors as important explanatory components for the establishment
and persistence of this invasive monocot. However, controlled studies specifically targeting water relations in M. vimineum are needed. Therefore, the purpose of this study was to determine how different water availabilities influence the growth
and physiological performance of M. vimineum. This study utilized experimental microcosms to achieve different water availabilities including low soil moisture (<15%
water), moderate soil moisture (ca. 20–30%), and flooded conditions. While both flooded and low soil moisture resulted in
diminished growth, M. vimineum still survived under these conditions. Physiological processes including C4 metabolism, minimum stress under low water conditions, and the ability to increase tissue rigidity may confer some advantages
to M. vimineum during periods of limiting water conditions. Similarly, the proportionally low root biomass, shallow root structure, and
its ability to maintain stable water relations during flooding and/or soil waterlogging may facilitate M. vimineum’s ability to invade mesic habitats. It is likely, therefore, that the capacity to tolerate both low soil moistures and flooded
conditions has enhanced the ability of M. vimineum to populate disturbed systems in central North Carolina. 相似文献
3.
Thorsten Thye Genevieve Scarisbrick Edmund N. L. Browne Margaret Amanua Chinbuah John Gyapong Ivy Osei Ellis Owusu-Dabo Stefan Niemann Sabine Rüsch-Gerdes Christian G. Meyer Rolf D. Horstmann 《PloS one》2009,4(7)
The gene of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4), a negative regulator of T lymphocytes, contains a single-nucleotide polymorphism (SNP) at position +6230A->G (ct60A->G), which has been found associated with several autoimmune diseases and appears to reduce T-cell inhibitory activity. In Ghana, West Africa, we compared the frequencies of CTLA4 +6230 A/G and 6 haplotype-tagging SNPs in 2010 smear-positive, HIV-negative patients with pulmonary tuberculosis (TB) and 2346 controls matched for age, gender and ethnicity. We found no difference in allele frequencies between cases and controls. However, +6230A and a distinct CTLA4 haplotype and a diplotype comprising the +6230A allele were significantly less frequent among cases with large opacities in chest radiographs compared to those with small ones (Pcorrected [cor] = 0.002, Pcor = 0.00045, P = 0.0005, respectively). This finding suggests that an increased T-cell activity associated with the CTLA4 +6230G allele contributes to pathology rather than to protection in pulmonary TB. 相似文献
4.
Damien Sanlaville Capucine Delnatte Jean-Franois Mougenot Joris-Robert Vermeesch Claude Houdayer Marie-Christine de
Blois David Genevieve Olivier Goulet Jean-Pierre Fryns Francis Jaubert Michel Vekemans Stanislas Lyonnet Serge Romana Charis Eng Dominique Stoppa-Lyonnet 《American journal of human genetics》2006,79(3):596-597
5.
Miriam Rossi Francesco Caruso Erica J. Crespi Jens Z. Pedersen Gail Nakano Michelle Duong Celia Mckee Sharon Lee Manasi Jiwrajka Charles Caldwell Francis Baffour Dylan Alex Karlin Genevieve Lidoff Stefano Leone Valentina Balducci Jaroslav Miler Sandra Incerpi 《Biochimie》2013
In order to better understand the antioxidant behavior of a series of polyphenolic 2′-hydroxychalcones, we describe the results of several chemical and biological studies, in vitro and in vivo. Single crystal X-ray methods elucidated their molecular structures and important intermolecular interactions such as H-bonding and molecular stacking in the crystal structures that contribute to our knowledge in explaining antioxidant activity. The results of experiments using the 1,1-diphenyl-2-dipicrylhydrazyl (DPPH) UV–vis spectroscopic method indicate that a hydroxyl group in position 5′ induces the highest antioxidant activity. Consequently, 2,2′,5′-trihydroxychalcone was selected for further study in vitro towards ROS scavenging in L-6 myoblasts and THP-1 human monocytes, where it shows an excellent antioxidant activity in a concentration range lower than that reported by most studies of related molecules. In addition, this chalcone shows a very selective activity: it inhibits the proliferation of leukemic cells, but it does not affect the normal L-6 myoblasts and human fibroblasts. In studying 2,2′,5′-trihydroxychalcone's effect on weight gain and serum glucose and insulin levels in Zucker fatty (fa−/fa−) rats we found that supplementing the diet with a 10 mg/kg dose of this chalcone (3 times weekly) blunted the increase in glucose that co-occurs with weight gain over the 6-week treatment period. It is concluded that 2,2′,5′-trihydroxychalcone has the potential to serve as a protective agent for some debilitating diseases. 相似文献
6.
Genevieve G. A. Fouda Joshua D. Amos Andrew B. Wilks Justin Pollara Caroline A. Ray Anjali Chand Erika L. Kunz Brooke E. Liebl Kaylan Whitaker Angela Carville Shannon Smith Lisa Colvin David J. Pickup Herman F. Staats Glenn Overman Krissey Eutsey-Lloyd Robert Parks Haiyan Chen Celia LaBranche Susan Barnett Georgia D. Tomaras Guido Ferrari David C. Montefiori Hua-Xin Liao Norman L. Letvin Barton F. Haynes Sallie R. Permar 《Journal of virology》2013,87(12):6986-6999
We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody responses in milk, hormone-induced lactating rhesus monkeys were vaccinated with a transmitted/founder (T/F) HIV Env immunogen in a prime-boost strategy modeled after the moderately protective RV144 HIV vaccine. Lactating rhesus monkeys were intramuscularly primed with either recombinant DNA (n = 4) or modified vaccinia virus Ankara (MVA) poxvirus vector (n = 4) expressing the T/F HIV Env C.1086 and then boosted twice intramuscularly with C.1086 gp120 and the adjuvant MF59. The vaccines induced Env-binding IgG and IgA as well as neutralizing and antibody-dependent cellular cytotoxicity (ADCC) responses in plasma and milk of most vaccinated animals. Importantly, plasma neutralization titers against clade C HIV variants MW965 (P = 0.03) and CAP45 (P = 0.04) were significantly higher in MVA-primed than in DNA-primed animals. The superior systemic prime-boost regimen was then compared to a mucosal-boost regimen, in which animals were boosted twice intranasally with C.1086 gp120 and the TLR 7/8 agonist R848 following the same systemic prime. While the systemic and mucosal vaccine regimens elicited comparable levels of Env-binding IgG antibodies, mucosal immunization induced significantly stronger Env-binding IgA responses in milk (P = 0.03). However, the mucosal regimen was not as potent at inducing functional IgG responses. This study shows that systemic MVA prime followed by either intranasal or systemic protein boosts can elicit strong humoral responses in breast milk and may be a useful strategy to interrupt postnatal HIV-1 transmission. 相似文献
7.
Joshua N. Cobb Genevieve DeClerck Anthony Greenberg Randy Clark Susan McCouch 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2013,126(4):867-887
More accurate and precise phenotyping strategies are necessary to empower high-resolution linkage mapping and genome-wide association studies and for training genomic selection models in plant improvement. Within this framework, the objective of modern phenotyping is to increase the accuracy, precision and throughput of phenotypic estimation at all levels of biological organization while reducing costs and minimizing labor through automation, remote sensing, improved data integration and experimental design. Much like the efforts to optimize genotyping during the 1980s and 1990s, designing effective phenotyping initiatives today requires multi-faceted collaborations between biologists, computer scientists, statisticians and engineers. Robust phenotyping systems are needed to characterize the full suite of genetic factors that contribute to quantitative phenotypic variation across cells, organs and tissues, developmental stages, years, environments, species and research programs. Next-generation phenotyping generates significantly more data than previously and requires novel data management, access and storage systems, increased use of ontologies to facilitate data integration, and new statistical tools for enhancing experimental design and extracting biologically meaningful signal from environmental and experimental noise. To ensure relevance, the implementation of efficient and informative phenotyping experiments also requires familiarity with diverse germplasm resources, population structures, and target populations of environments. Today, phenotyping is quickly emerging as the major operational bottleneck limiting the power of genetic analysis and genomic prediction. The challenge for the next generation of quantitative geneticists and plant breeders is not only to understand the genetic basis of complex trait variation, but also to use that knowledge to efficiently synthesize twenty-first century crop varieties. 相似文献
8.
9.
Female mate preferences for ecologically relevant traits may enhance natural selection, leading to rapid divergence. They may also forge a link between mate choice within species and sexual isolation between species. Here, we examine female mate preference for two ecologically important traits: body size and body shape. We measured female preferences within and between species of benthic, limnetic, and anadromous threespine sticklebacks (Gasterosteus aculeatus species complex). We found that mate preferences differed between species and between contexts (i.e., within vs. between species). Within species, anadromous females preferred males that were deep bodied for their size, benthic females preferred larger males (as measured by centroid size), and limnetic females preferred males that were more limnetic shaped. In heterospecific mating trials between benthics and limnetics, limnetic females continued to prefer males that were more limnetic like in shape when presented with benthic males. Benthic females showed no preferences for size when presented with limnetic males. These results show that females use ecologically relevant traits to select mates in all three species and that female preference has diverged between species. These results suggest that sexual selection may act in concert with natural selection on stickleback size and shape. Further, our results suggest that female preferences may track adaptation to local environments and contribute to sexual isolation between benthic and limnetic sticklebacks. 相似文献
10.
Keith K. Fenrich Pascal Weber Genevieve Rougon Franck Debarbieux 《Journal of visualized experiments : JoVE》2013,(82)
Experimental autoimmune encephalomyelitis (EAE) in adult rodents is the standard experimental model for studying autonomic demyelinating diseases such as multiple sclerosis. Here we present a low-cost and reproducible glass window implantation protocol that is suitable for intravital microscopy and studying the dynamics of spinal cord cytoarchitecture with subcellular resolution in live adult mice with EAE. Briefly, we surgically expose the vertebrae T12-L2 and construct a chamber around the exposed vertebrae using a combination of cyanoacrylate and dental cement. A laminectomy is performed from T13 to L1, and a thin layer of transparent silicone elastomer is applied to the dorsal surface of the exposed spinal cord. A modified glass cover slip is implanted over the exposed spinal cord taking care that the glass does not directly contact the spinal cord. To reduce the infiltration of inflammatory cells between the window and spinal cord, anti-inflammatory treatment is administered every 2 days (as recommended by ethics committee) for the first 10 days after implantation. EAE is induced only 2-3 weeks after the cessation of anti-inflammatory treatment.Using this approach we successfully induced EAE in 87% of animals with implanted windows and, using Thy1-CFP-23 mice (blue axons in dorsal spinal cord), quantified axonal loss throughout EAE progression. Taken together, this protocol may be useful for studying the recruitment of various cell populations as well as their interaction dynamics, with subcellular resolution and for extended periods of time. This intravital imaging modality represents a valuable tool for developing therapeutic strategies to treat autoimmune demyelinating diseases such as EAE. 相似文献