全文获取类型
收费全文 | 1544篇 |
免费 | 139篇 |
专业分类
1683篇 |
出版年
2023年 | 9篇 |
2022年 | 41篇 |
2021年 | 72篇 |
2020年 | 29篇 |
2019年 | 38篇 |
2018年 | 36篇 |
2017年 | 33篇 |
2016年 | 61篇 |
2015年 | 93篇 |
2014年 | 83篇 |
2013年 | 96篇 |
2012年 | 138篇 |
2011年 | 120篇 |
2010年 | 67篇 |
2009年 | 61篇 |
2008年 | 80篇 |
2007年 | 74篇 |
2006年 | 65篇 |
2005年 | 65篇 |
2004年 | 59篇 |
2003年 | 51篇 |
2002年 | 45篇 |
2001年 | 21篇 |
2000年 | 22篇 |
1999年 | 19篇 |
1998年 | 7篇 |
1997年 | 4篇 |
1996年 | 6篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 10篇 |
1991年 | 9篇 |
1990年 | 6篇 |
1989年 | 7篇 |
1988年 | 7篇 |
1987年 | 6篇 |
1985年 | 8篇 |
1984年 | 7篇 |
1983年 | 4篇 |
1981年 | 5篇 |
1980年 | 10篇 |
1978年 | 7篇 |
1975年 | 8篇 |
1974年 | 5篇 |
1973年 | 6篇 |
1971年 | 7篇 |
1966年 | 3篇 |
1961年 | 3篇 |
1957年 | 3篇 |
1912年 | 3篇 |
排序方式: 共有1683条查询结果,搜索用时 15 毫秒
91.
E. Hesse A. Best M. Boots A. R. Hall A. Buckling 《Journal of evolutionary biology》2015,28(9):1682-1690
Abiotic environmental heterogeneity can promote the evolution of diverse resource specialists, which in turn may increase the degree of host–parasite specialization. We coevolved Pseudomonas fluorescens and lytic phage ?2 in spatially structured populations, each consisting of two interconnected subpopulations evolving in the same or different nutrient media (homogeneous and heterogeneous environments, respectively). Counter to the normal expectation, host–parasite specialization was significantly lower in heterogeneous compared with homogeneous environments. This result could not be explained by dispersal homogenizing populations, as this would have resulted in the heterogeneous treatments having levels of specialization equal to or greater than that of the homogeneous environments. We argue that selection for costly generalists is greatest when the coevolving species are exposed to diverse environmental conditions and that this can provide an explanation for our results. A simple coevolutionary model of this process suggests that this can be a general mechanism by which environmental heterogeneity can reduce rather than increase host–parasite specialization. 相似文献
92.
The tenth annual Keystone Symposium on the Mechanism and Biology of Silencing convened in Monterey, California, in March 2011. Those seeking some West Coast sunshine were, unfortunately, met with incessant precipitation throughout the meeting. Nevertheless, attendees were brightened by enlightening and vigorous scientific discussions. Here, we summarize the results presented at the meeting, which inspire and push this expanding field into new territories. 相似文献
93.
Hatton O Phillips LK Vaysberg M Hurwich J Krams SM Martinez OM 《The Journal of biological chemistry》2011,286(43):37368-37378
B cell lymphoma survival requires tonic or ligand-independent signals through activation of Syk by the B cell receptor. The Epstein-Barr virus (EBV) protein latent membrane 2a (LMP2a), a mimic of the B cell receptor, provides constitutive survival signals for latently infected cells through Syk activation; however, the precise downstream mechanisms coordinating this survival response in EBV+ B cell lymphomas remain to be elucidated. Herein, we assess the mechanism of Syk survival signaling in EBV+ B cell lymphomas from post-transplant lymphoproliferative disorder (PTLD) to discover virally controlled therapeutic targets involved in lymphomagenesis and tumor progression. Using small molecule inhibition and siRNA strategies, we show that Syk inhibition reduces proliferation and induces apoptosis of PTLD-derived EBV+ B cell lines. Syk inhibition also reduces autocrine IL-10 production. Although Syk inhibition attenuates signaling through both the PI3K/Akt and Erk pathways, only PI3K/Akt inhibition causes apoptosis of PTLD-derived cell lines. Loss of the endogenous caspase inhibitor XIAP is observed after Syk or PI3K/Akt inhibition. The loss of XIAP and apoptosis that results from Syk or PI3K/Akt inhibition is reversed by inhibition of the mitochondrial protease HtrA2. Thus, Syk drives EBV+ B cell lymphoma survival through PI3K/Akt activation, which prevents the HtrA2-dependent loss of XIAP. Syk, Akt, and XIAP antagonists may present potential new therapeutic strategies for PTLD through targeting of EBV-driven survival signals. 相似文献
94.
Simkin AJ Guirimand G Papon N Courdavault V Thabet I Ginis O Bouzid S Giglioli-Guivarc'h N Clastre M 《Planta》2011,234(5):903-914
In plants, the mevalonic acid (MVA) pathway provides precursors for the formation of triterpenes, sesquiterpenes, phytosterols
and primary metabolites important for cell integrity. Here, we have cloned the cDNA encoding enzymes catalysing the final
three steps of the MVA pathway from Madagascar periwinkle (Catharanthus roseus), mevalonate kinase (MVK), 5-phosphomevalonate kinase (PMK) and mevalonate 5-diphosphate decarboxylase (MVD). These cDNA were
shown to functionally complement MVA pathway deletion mutants in the yeast Saccharomyces cerevisiae. Transient transformations of C. roseus cells with yellow fluorescent protein (YFP)-fused constructs reveal that PMK and MVD are localised to the peroxisomes, while
MVK was cytosolic. These compartmentalisation results were confirmed using the Arabidopsis thaliana MVK, PMK and MVD sequences fused to YFP. Based on these observations and the arguments raised here we conclude that the final
steps of the plant MVA pathway are localised to the peroxisome. 相似文献
95.
This study investigated the spatial, spectral, temporal and functional proprieties of functional brain connections involved in the concurrent execution of unrelated visual perception and working memory tasks. Electroencephalography data was analysed using a novel data-driven approach assessing source coherence at the whole-brain level. Three connections in the beta-band (18-24 Hz) and one in the gamma-band (30-40 Hz) were modulated by dual-task performance. Beta-coherence increased within two dorsofrontal-occipital connections in dual-task conditions compared to the single-task condition, with the highest coherence seen during low working memory load trials. In contrast, beta-coherence in a prefrontal-occipital functional connection and gamma-coherence in an inferior frontal-occipitoparietal connection was not affected by the addition of the second task and only showed elevated coherence under high working memory load. Analysis of coherence as a function of time suggested that the dorsofrontal-occipital beta-connections were relevant to working memory maintenance, while the prefrontal-occipital beta-connection and the inferior frontal-occipitoparietal gamma-connection were involved in top-down control of concurrent visual processing. The fact that increased coherence in the gamma-connection, from low to high working memory load, was negatively correlated with faster reaction time on the perception task supports this interpretation. Together, these results demonstrate that dual-task demands trigger non-linear changes in functional interactions between frontal-executive and occipitoparietal-perceptual cortices. 相似文献
96.
Poor context integration, the process of incorporating both previous and current information in decision making, is a cognitive symptom of schizophrenia. The maintenance of the contextual information has been shown to be sensitive to changes in excitation-inhibition (EI) balance. Many regions of the brain are sensitive to EI imbalances, however, so it is unknown how systemic manipulations affect the specific regions that are important to context integration. We constructed a multi-structure, biophysically-realistic agent that could perform context-integration as is assessed by the dot pattern expectancy task. The agent included a perceptual network, a memory network, and a decision making system and was capable of successfully performing the dot pattern expectancy task. Systemic manipulation of the agent’s EI balance produced localized dysfunction of the memory structure, which resulted in schizophrenia-like deficits at context integration. When the agent’s pyramidal cells were less excitatory, the agent fixated upon the cue and initiated responding later than the default agent, which were like the deficits one would predict that individuals on the autistic spectrum would make. This modelling suggests that it may be possible to parse between different types of context integration deficits by adding distractors to context integration tasks and by closely examining a participant’s reaction times. 相似文献
97.
Olivia L. Mooren Joanna Kim Jinmei Li John A. Cooper 《The Journal of biological chemistry》2015,290(30):18796-18805
Endothelial cells (ECs) form a monolayer that serves as a barrier between the blood and the underlying tissue. ECs tightly regulate their cell-cell junctions, controlling the passage of soluble materials and immune cells across the monolayer barrier. We studied the role of N-WASP, a key regulator of Arp2/3 complex and actin assembly, in EC monolayers. We report that N-WASP regulates endothelial monolayer integrity by affecting the organization of cell junctions. Depletion of N-WASP resulted in an increase in transendothelial electrical resistance, a measure of monolayer integrity. N-WASP depletion increased the width of cell-cell junctions and altered the organization of F-actin and VE-cadherin at junctions. N-WASP was not present at cell-cell junctions in monolayers under resting conditions, but it was recruited following treatment with sphingosine-1-phosphate. Taken together, our results reveal a novel role for N-WASP in remodeling EC junctions, which is critical for monolayer integrity and function. 相似文献
98.
Background and Aims
Male-biased sex allocation commonly occurs in wind-pollinated hermaphroditic plants, and is often positively associated with size, notably in terms of height. Currently, it is not well established whether a corresponding pattern holds for dioecious plants: do males of wind-pollinated species exhibit greater reproductive allocation than females? Here, sexual dimorphism is investigated in terms of life history trade-offs in a dioecious population of the wind-pollinated ruderal herb Mercurialis annua.Methods
The allocation strategies of males and females grown under different soil nutrient availability and competitive (i.e. no, male or female competitor) regimes were compared.Key Results
Male reproductive allocation increased disproportionately with biomass, and was greater than that of females when grown in rich soils. Sexual morphs differentially adjusted their reproductive allocation in response to local environmental conditions. In particular, males reduced their reproductive allocation in poor soils, whereas females increased theirs, especially when competing with another female rather than growing alone. Finally, males displayed smaller above-ground vegetative sizes than females, but neither nutrient availability nor competition had a strong independent effect on relative size disparities between the sexes.Conclusions
Selection appears to favour plasticity in reproductive allocation in dioecious M. annua, thereby maintaining a relatively constant size hierarchy between sexual morphs. In common with other dioecious species, there seems to be little divergence in the niches occupied by males and females of M. annua. 相似文献99.
Christoph Ott Henrik Martens Imam Hassouna Bárbara Oliveira Christian Erck Maria-Patapia Zafeiriou Ulla-Kaisa Peteri D?rte Hesse Simone Gerhart Bekir Altas Tekla Kolbow Herbert Stadler Hiroshi Kawabe Wolfram-Hubertus Zimmermann Klaus-Armin Nave Walter Schulz-Schaeffer Olaf Jahn Hannelore Ehrenreich 《Molecular medicine (Cambridge, Mass.)》2015,21(1):803-815
Erythropoietin (EPO) exerts potent neuroprotective, neuroregenerative and procognitive functions. However, unequivocal demonstration of erythropoietin receptor (EPOR) expression in brain cells has remained difficult since previously available anti-EPOR antibodies (EPOR-AB) were unspecific. We report here a new, highly specific, polyclonal rabbit EPOR-AB directed against different epitopes in the cytoplasmic tail of human and murine EPOR and its characterization by mass spectrometric analysis of immuno-precipitated endogenous EPOR, Western blotting, immunostaining and flow cytometry. Among others, we applied genetic strategies including overexpression, Lentivirus-mediated conditional knockout of EpoR and tagged proteins, both on cultured cells and tissue sections, as well as intracortical implantation of EPOR-transduced cells to verify specificity. We show examples of EPOR expression in neurons, oligodendroglia, astrocytes and microglia. Employing this new EPOR-AB with double-labeling strategies, we demonstrate membrane expression of EPOR as well as its localization in intracellular compartments such as the Golgi apparatus. Moreover, we show injury-induced expression of EPOR. In mice, a stereotactically applied stab wound to the motor cortex leads to distinct EpoR expression by reactive GFAP-expressing cells in the lesion vicinity. In a patient suffering from epilepsy, neurons and oligodendrocytes of the hippocampus strongly express EPOR. To conclude, this new analytical tool will allow neuroscientists to pinpoint EPOR expression in cells of the nervous system and to better understand its role in healthy conditions, including brain development, as well as under pathological circumstances, such as upregulation upon distress and injury. 相似文献
100.
Olivia Harvey 《New genetics and society》2013,32(2):125-136
Abstract Over 12 months prior to the recent United Nations decision to defer a decision about what type of international treaty should be developed in the global stem-cell research and human cloning debate, the Federal Parliament of Australia passed two separate pieces of legislation relating to both these concerns. After a five-year long process of community consultation, media spectacle and parliamentary debate, reproductive cloning has been banned in Australia and only embryos considered to be excess to assisted reproductive technologies in existence on the 5th of April 2002 are currently valid research material. This paper argues that underpinning both pieces of legislation is a profound belief in the disruptive potential of all types of human cloning for the very nature and integrity of human species being. A belief, moreover, that is based on a presumption that it is apparently possible to conceptualise what being human even means for all Australians. 相似文献