全文获取类型
收费全文 | 3143篇 |
免费 | 262篇 |
国内免费 | 2篇 |
专业分类
3407篇 |
出版年
2023年 | 12篇 |
2022年 | 43篇 |
2021年 | 64篇 |
2020年 | 33篇 |
2019年 | 49篇 |
2018年 | 78篇 |
2017年 | 54篇 |
2016年 | 119篇 |
2015年 | 174篇 |
2014年 | 182篇 |
2013年 | 206篇 |
2012年 | 289篇 |
2011年 | 266篇 |
2010年 | 167篇 |
2009年 | 156篇 |
2008年 | 188篇 |
2007年 | 209篇 |
2006年 | 167篇 |
2005年 | 164篇 |
2004年 | 130篇 |
2003年 | 122篇 |
2002年 | 131篇 |
2001年 | 26篇 |
2000年 | 11篇 |
1999年 | 27篇 |
1998年 | 28篇 |
1997年 | 28篇 |
1996年 | 15篇 |
1995年 | 12篇 |
1994年 | 17篇 |
1993年 | 16篇 |
1992年 | 18篇 |
1991年 | 15篇 |
1990年 | 10篇 |
1989年 | 5篇 |
1988年 | 5篇 |
1987年 | 5篇 |
1985年 | 15篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 10篇 |
1974年 | 6篇 |
1971年 | 4篇 |
1969年 | 4篇 |
1960年 | 4篇 |
1957年 | 5篇 |
1953年 | 4篇 |
1946年 | 4篇 |
排序方式: 共有3407条查询结果,搜索用时 15 毫秒
91.
Esther E. Biswas-Fiss Stephanie Affet Malissa Ha Subhasis B. Biswas 《The Journal of biological chemistry》2012,287(53):44097-44107
The retina-specific ATP binding cassette transporter, ABCA4 protein, is associated with a broad range of inherited macular degenerations, including Stargardt disease, autosomal recessive cone rod dystrophy, and fundus flavimaculatus. In order to understand its role in retinal transport in rod out segment discs, we have investigated the interactions of the soluble domains of ABCA4 with both 11-cis- and all-trans-retinal. Using fluorescence anisotropy-based binding analysis and recombinant polypeptides derived from the amino acid sequences of the four soluble domains of ABCA4, we demonstrated that the nucleotide binding domain 1 (NBD1) specifically bound 11-cis-retinal. Its affinity for all-trans-retinal was markedly reduced. Stargardt disease-associated mutations in this domain resulted in attenuation of 11-cis-retinal binding. Significant differences in 11-cis-retinal binding affinities were observed between NBD1 and other cytoplasmic and lumenal domains of ABCA4. The results suggest a possible role of ABCA4 and, in particular, the NBD1 domain in 11-cis-retinal binding. These results also correlate well with a recent report on the in vivo role of ABCA4 in 11-cis-retinal transport. 相似文献
92.
Werth E Achermann P Borbély AA 《American journal of physiology. Regulatory, integrative and comparative physiology》2002,283(2):R527-R532
One of the hallmarks of rapid eye movement (REM) sleep is muscle atonia. Here we report extended epochs of muscle atonia in non-REM sleep (MAN). Their extent and time course was studied in a protocol that included a baseline night, a daytime sleep episode with or without selective REM sleep deprivation, and a recovery night. The distribution of the latency to the first occurrence of MAN was bimodal with a first mode shortly after sleep onset and a second mode 40 min later. Within a non-REM sleep episode, MAN showed a U-shaped distribution with the highest values before and after REM sleep. Whereas MAN was at a constant level over consecutive 2-h intervals of nighttime sleep, MAN showed high initial values when sleep began in the morning. Selective daytime REM sleep deprivation caused an initial enhancement of MAN during recovery sleep. It is concluded that episodes of MAN may represent an REM sleep equivalent and that it may be a marker of homeostatic and circadian REM sleep regulating processes. MAN episodes may contribute to the compensation of an REM sleep deficit. 相似文献
93.
Synthesis and antifungal activity of diverse C-2 pyridinyl and pyridinylvinyl substituted quinolines
Vladimir V. Kouznetsov Carlos M. Meléndez Gómez Marcos G. Derita Laura Svetaz Esther del Olmo Susana A. Zacchino 《Bioorganic & medicinal chemistry》2012,20(21):6506-6512
Diverse 2-pyridinyl quinolines 6–12 and 2-pyridinilvinyl quinolines 13–17 were prepared using a straightforward synthesis based on the BiCl3-catalyzed multicomponent imino Diels–Alder (imino DA) reaction or a novel tandem imino DA/catalytic tetrahydroquinoline ring oxidation/Perkin condensation sequential process. All members of the series showed activities against dermatophytes and some of them possessed a broad spectrum of action. 2-(Pyridin-4-yl)quinoline 9 and 2-(2-pyridin-4-yl)vinyl)quinoline 16 showed the best MIC80 and MIC50 against the clinically important fungi Candida albicans and non-albicans Candida species. In turn, 6-ethyl-2-(pyridin-2-yl)quinoline 6 showed the best properties against standardized as well as clinical strains of Cryptococcus neoformans. 相似文献
94.
Vitellin and vitellogenin labelled in vitro with 125I and in vivo with 3H were incorporated into yolk by locust oöcytes incubated in an in vitro system. This incorporation was specific and linear with the duration of incubation. Uptake of vitellin by oöcytes was 3–4 times higher than 125I-bovine serum albumin in 2.1-mm oöcytes and 20 times higher than 125I-bovine serum albumin in 4.0-mm long oöcytes. The uptake of the albumin was enhanced by the presence of vitellin in the incubation medium. 3H-labelled yolk protein was incorporated at higher rates than that labelled with 125I. The addition of the juvenile hormone analogue ZR 515, caused the incorporation rates of vitellogenin to be increased. The amount of vitellin or vitellogenin taken up by the oöcytes increased with their length, and the rate of incorporation per unit surface area was highest in 3–4-mm long oöcytes. These results corroborate previously reported in vivo patterns of incorporation rates of developing oöcytes. 相似文献
95.
Differential transmission of human immunodeficiency virus type 1 by distinct subsets of effector dendritic cells 总被引:6,自引:0,他引:6
Sanders RW de Jong EC Baldwin CE Schuitemaker JH Kapsenberg ML Berkhout B 《Journal of virology》2002,76(15):7812-7821
Dendritic cells (DC) support human immunodeficiency virus type 1 (HIV-1) transmission by capture of the virus particle in the mucosa and subsequent transport to the draining lymph node, where HIV-1 is presented to CD4(+) Th cells. Virus transmission involves a high-affinity interaction between the DC-specific surface molecule DC-SIGN and the viral envelope glycoprotein gp120 and subsequent internalization of the virus, which remains infectious. The mechanism of viral transmission from DC to T cells is currently unknown. Sentinel immature DC (iDC) develop into Th1-promoting effector DC1 or Th2-promoting DC2, depending on the activation signals. We studied the ability of these effector DC subsets to support HIV-1 transmission in vitro. Compared with iDC, virus transmission is greatly upregulated for the DC1 subset, whereas DC2 cells are inactive. Increased transmission by DC1 correlates with increased expression of ICAM-1, and blocking studies confirm that ICAM-1 expression on DC is important for HIV transmission. The ICAM-1-LFA-1 interaction is known to be important for immunological cross talk between DC and T cells, and our results indicate that this cell-cell contact is exploited by HIV-1 for efficient transmission. 相似文献
96.
Abstract: The relationship between elevations in intracellular free Ca2+ concentration ([Ca2+]i) by different mechanisms and tyrosine hydroxylase (TH) gene expression was examined. Depolarization by an elevated K+ concentration triggered rapid and sustained increases in [Ca2+]i from a basal level of ~50 to 110–150 nM and three- to fourfold elevations in TH mRNA levels, requiring extracellular calcium but not inositol 1,4,5-trisphosphate (IP3). On the other hand, bradykinin or thapsigargin, both of which induce release of intracellular calcium stores via IP3 or inhibition of Ca2+-ATPase, rapidly elevated [Ca2+]i to >200 nM and increased TH gene expression (three-to fivefold). Confocal imaging showed that the elevations in [Ca2+]i in each case occurred throughout the cyto- and nucleoplasm. The initial rise in [Ca2+]i due to either bradykinin or thapsigargin, which did not require extracellular calcium, was sufficient to initiate the events leading to increased TH expression. Consistent with this, the effects of bradykinin on TH expression were inhibited by 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid or 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester which chelates or inhibits the release of intracellular calcium, respectively. Bradykinin required a rise in [Ca2+]i for <10 min, as opposed to 10–30 min for depolarization to increase TH mRNA levels. These results demonstrate that although each of these treatments increased TH gene expression by raising [Ca2+]i, there are important differences among them in terms of the magnitude of elevated [Ca2+]i, requirements for extracellular calcium or release of intracellular calcium stores, and duration of elevated [Ca2+]i, indicating the involvement of different calcium signaling pathways leading to regulation of TH gene expression. 相似文献
97.
Sameh Sassi Samir Aydi Esther M. Gonzalez Cesar Arrese-Igor Chedly Abdelly 《Symbiosis (Philadelphia, Pa.)》2010,52(1):1-10
Drought and salinity are environmental constraints that affect crop yields worldwide. In nature, both stresses are multifaceted
problems that are usually associated with other adverse circumstances which limit plant performance such as water shortage
and nutrient deficits. In order to assess common features of both stresses, the effects of mannitol-induced osmotic stress
were monitored using two Phaseolus vulgaris cultivars, Cv. ‘Flamingo’ (tolerant) and Cv. ‘Coco Blanc’ (sensitive) which differed in their drought and salinity tolerance.
Growth, water relations, organic and inorganic compound accumulation and soluble protein contents were measured in leaves
and nodules of these N2-fixing plants. The aim of the present study was to check whether osmotic stress tolerance is associated with accumulation
of some of these compounds either in leaves, nodules or both organs. At the whole-plant level, Cv. ‘Flamingo’ showed a better
maintenance of plant biomass and shoot water status. At the cell level, this was related to a better osmotic adjustment ability
both in leaves and nodules and also to a better adjustment of the cell wall elasticity. At the metabolic level, the contrasting
accumulation of the different amino acids in nodules of each cultivar suggested that amino acids pathways can be regulated
to different degrees under stress conditions. At the metabolic level, it seems that symbiosis in the sink organ (the nodule)
plays a crucial role in conferring drought and salinity tolerance in the common bean. 相似文献
98.
Hira Sharanpreet Packialakshmi Balamurugan Tang Esther Zhou Xiaoming 《Journal of physiology and biochemistry》2021,77(1):1-11
Journal of Physiology and Biochemistry - Dexamethasone augments mitochondrial protein abundance. The translocase of the outer membrane (Tom) of mitochondria plays a major role in importing largely... 相似文献
99.
Historical Biogeography of endemic seed plant genera in the Caribbean: Did GAARlandia play a role? 下载免费PDF全文
María Esther Nieto‐Blázquez Alexandre Antonelli Julissa Roncal 《Ecology and evolution》2017,7(23):10158-10174
The Caribbean archipelago is a region with an extremely complex geological history and an outstanding plant diversity with high levels of endemism. The aim of this study was to better understand the historical assembly and evolution of endemic seed plant genera in the Caribbean, by first determining divergence times of endemic genera to test whether the hypothesized Greater Antilles and Aves Ridge (GAARlandia) land bridge played a role in the archipelago colonization and second by testing South America as the main colonization source as expected by the position of landmasses and recent evidence of an asymmetrical biotic interchange. We reconstructed a dated molecular phylogenetic tree for 625 seed plants including 32 Caribbean endemic genera using Bayesian inference and ten calibrations. To estimate the geographic range of the ancestors of endemic genera, we performed a model selection between a null and two complex biogeographic models that included timeframes based on geological information, dispersal probabilities, and directionality among regions. Crown ages for endemic genera ranged from Early Eocene (53.1 Ma) to Late Pliocene (3.4 Ma). Confidence intervals for divergence times (crown and/or stem ages) of 22 endemic genera occurred within the GAARlandia time frame. Contrary to expectations, the Antilles appears as the main ancestral area for endemic seed plant genera and only five genera had a South American origin. In contrast to patterns shown for vertebrates and other organisms and based on our sampling, we conclude that GAARlandia did not act as a colonization route for plants between South America and the Antilles. Further studies on Caribbean plant dispersal at the species and population levels will be required to reveal finer‐scale biogeographic patterns and mechanisms. 相似文献
100.
Cohen-Hadar N Wine Y Nachliel E Huppert D Gutman M Frolow F Freeman A 《Biotechnology and bioengineering》2006,94(5):1005-1011
Protein crystals, routinely prepared for the elucidation of protein 3D structures by X-ray crystallography, present an ordered and highly accurate 3D array of protein molecules. Inherent to the 3D arrangement of the protein molecules in the crystal is a complementary 3D array of voids made of interconnected cavities and exhibiting highly ordered porosity. The permeability of the porosity of chemically crosslinked enzyme protein crystals to low molecular weight solutes, was used for enzyme mediated organic synthesis and size exclusion chromatography. This permeability might be extended to explore new potential applications for protein crystals, for example, their use as bio-templates for the fabrication of novel, nano-structured composite materials. The quality of composites obtained from "filling" of the ordered voids in protein crystals and their potential applications will be strongly dependent upon an accurate preservation of the order in the original protein crystal 3D array during the "filling" process. Here we propose and demonstrate the feasibility of monitoring the changes in 3D order of the protein array by a step-by-step molecular level monitoring of a model system for hydrogel bio-templating by glutaraldehyde crosslinked lysozyme crystals. This monitoring is based on step-by-step comparative analysis of data obtained from (i) X-ray crystallography: resolution, unit cell dimensions and B-factor values and (ii) fluorescence decay kinetics of ultra-fast laser activated dye, impregnated within these crystals. Our results demonstrated feasibility of the proposed monitoring approach and confirmed that the stabilized protein crystal template retained its 3D structure throughout the process. 相似文献