全文获取类型
收费全文 | 4991篇 |
免费 | 563篇 |
出版年
2021年 | 70篇 |
2020年 | 46篇 |
2019年 | 48篇 |
2018年 | 61篇 |
2017年 | 66篇 |
2016年 | 113篇 |
2015年 | 174篇 |
2014年 | 176篇 |
2013年 | 267篇 |
2012年 | 278篇 |
2011年 | 318篇 |
2010年 | 204篇 |
2009年 | 170篇 |
2008年 | 239篇 |
2007年 | 231篇 |
2006年 | 210篇 |
2005年 | 198篇 |
2004年 | 196篇 |
2003年 | 183篇 |
2002年 | 199篇 |
2001年 | 117篇 |
2000年 | 103篇 |
1999年 | 116篇 |
1998年 | 59篇 |
1997年 | 49篇 |
1996年 | 63篇 |
1995年 | 54篇 |
1994年 | 58篇 |
1993年 | 64篇 |
1992年 | 65篇 |
1991年 | 53篇 |
1990年 | 70篇 |
1989年 | 88篇 |
1988年 | 56篇 |
1987年 | 41篇 |
1986年 | 47篇 |
1985年 | 49篇 |
1984年 | 50篇 |
1983年 | 44篇 |
1982年 | 56篇 |
1981年 | 41篇 |
1980年 | 37篇 |
1979年 | 49篇 |
1978年 | 33篇 |
1977年 | 35篇 |
1976年 | 49篇 |
1975年 | 33篇 |
1974年 | 52篇 |
1973年 | 42篇 |
1971年 | 32篇 |
排序方式: 共有5554条查询结果,搜索用时 15 毫秒
991.
992.
Bradley A. Heller Monica Ghidinelli Jakob Voelkl Steven Einheber Ryan Smith Ethan Grund Grant Morahan David Chandler Luba Kalaydjieva Filippo Giancotti Rosalind H. King Aniko Naray Fejes-Toth Gerard Fejes-Toth Maria Laura Feltri Florian Lang James L. Salzer 《The Journal of cell biology》2014,204(7):1219-1236
The PI 3-kinase (PI 3-K) signaling pathway is essential for Schwann cell myelination. Here we have characterized PI 3-K effectors activated during myelination by probing myelinating cultures and developing nerves with an antibody that recognizes phosphorylated substrates for this pathway. We identified a discrete number of phospho-proteins including the S6 ribosomal protein (S6rp), which is down-regulated at the onset of myelination, and N-myc downstream-regulated gene-1 (NDRG1), which is up-regulated strikingly with myelination. We show that type III Neuregulin1 on the axon is the primary activator of S6rp, an effector of mTORC1. In contrast, laminin-2 in the extracellular matrix (ECM), signaling through the α6β4 integrin and Sgk1 (serum and glucocorticoid-induced kinase 1), drives phosphorylation of NDRG1 in the Cajal bands of the abaxonal compartment. Unexpectedly, mice deficient in α6β4 integrin signaling or Sgk1 exhibit hypermyelination during development. These results identify functionally and spatially distinct PI 3-K pathways: an early, pro-myelinating pathway driven by axonal Neuregulin1 and a later-acting, laminin–integrin-dependent pathway that negatively regulates myelination. 相似文献
993.
994.
995.
Vesna Tosic Diana L. Thomas David M. Kranz Jia Liu Grant McFadden Joanna L. Shisler Amy L. MacNeill Edward J. Roy 《PloS one》2014,9(10)
Myxoma virus, a rabbit poxvirus, can efficiently infect various types of mouse and human cancer cells. It is a strict rabbit-specific pathogen, and is thought to be safe as a therapeutic agent in all non-rabbit hosts tested including mice and humans. Interleukin-15 (IL15) is an immuno-modulatory cytokine with significant potential for stimulating anti-tumor T lymphocytes and NK cells. Co-expression of IL15 with the α subunit of IL15 receptor (IL15Rα) greatly enhances IL15 stability and bioavailability. Therefore, we engineered a new recombinant myxoma virus (vMyx-IL15Rα-tdTr), which expresses an IL15Rα-IL15 fusion protein plus tdTomato red fluorescent reporter protein. Permissive rabbit kidney epithelial (RK-13) cells infected with vMyx-IL15Rα-tdTr expressed and secreted the IL15Rα-IL15 fusion protein. Functional activity was confirmed by demonstrating that the secreted fusion protein stimulated proliferation of cytokine-dependent CTLL-2 cells. Multi-step growth curves showed that murine melanoma (B16-F10 and B16.SIY) cell lines were permissive to vMyx-IL15Rα-tdTr infection. In vivo experiments in RAG1-/- mice showed that subcutaneous B16-F10 tumors treated with vMyx-IL15Rα-tdTr exhibited attenuated tumor growth and a significant survival benefit for the treated group compared to the PBS control and the control viruses (vMyx-IL15-tdTr and vMyx-tdTr). Immunohistological analysis of the subcutaneous tumors showed dramatically increased infiltration of NK cells in vMyx-IL15Rα-tdTr treated tumors compared to the controls. In vivo experiments with immunocompetent C57BL/6 mice revealed a strong infiltrate of both NK cells and CD8+ T cells in response to vMyx-IL15Rα-tdTr, and prolonged survival. We conclude that delivery of IL15Rα-IL15 in a myxoma virus vector stimulates both innate and adaptive components of the immune system. 相似文献
996.
Moataz Abd El Ghany Jagadish Chander Ankur Mutreja Mamoon Rashid Grant A. Hill-Cawthorne Shahjahan Ali Raeece Naeem Nicholas R. Thomson Gordon Dougan Arnab Pain 《PLoS neglected tropical diseases》2014,8(7)
Background
Cholera infection continues to be a threat to global public health. The current cholera pandemic associated with Vibrio cholerae El Tor has now been ongoing for over half a century.Methodology/Principal Findings
Thirty-eight V. cholerae El Tor isolates associated with a cholera outbreak in 2009 from the Chandigarh region of India were characterised by a combination of microbiology, molecular typing and whole-genome sequencing. The genomic analysis indicated that two clones of V. cholera circulated in the region and caused disease during this time. These clones fell into two distinct sub-clades that map independently onto wave 3 of the phylogenetic tree of seventh pandemic V. cholerae El Tor. Sequence analyses of the cholera toxin gene, the Vibrio seventh Pandemic Island II (VSPII) and SXT element correlated with this phylogenetic position of the two clades on the El Tor tree. The clade 2 isolates, characterized by a drug-resistant profile and the expression of a distinct cholera toxin, are closely related to the recent V. cholerae isolated elsewhere, including Haiti, but fell on a distinct branch of the tree, showing they were independent outbreaks. Multi-Locus Sequence Typing (MLST) distinguishes two sequence types among the 38 isolates, that did not correspond to the clades defined by whole-genome sequencing. Multi-Locus Variable-length tandem-nucleotide repeat Analysis (MLVA) identified 16 distinct clusters.Conclusions/Significance
The use of whole-genome sequencing enabled the identification of two clones of V. cholerae that circulated during the 2009 Chandigarh outbreak. These clones harboured a similar structure of ICEVchHai1 but differed mainly in the structure of CTX phage and VSPII. The limited capacity of MLST and MLVA to discriminate between the clones that circulated in the 2009 Chandigarh outbreak highlights the value of whole-genome sequencing as a route to the identification of further genetic markers to subtype V. cholerae isolates. 相似文献997.
Two-photon laser scanning microscopy has revolutionized the ability to delineate cellular and physiological function in acutely isolated tissue and in
vivo. However, there exist barriers for many laboratories to acquire two-photon microscopes. Additionally, if owned, typical systems are difficult to modify to rapidly evolving methodologies. A potential solution to these problems is to enable scientists to build their own high-performance and adaptable system by overcoming a resource insufficiency. Here we present a detailed hardware resource and protocol for building an upright, highly modular and adaptable two-photon laser scanning fluorescence microscope that can be used for in
vitro or in
vivo applications. The microscope is comprised of high-end componentry on a skeleton of off-the-shelf compatible opto-mechanical parts. The dedicated design enabled imaging depths close to 1 mm into mouse brain tissue and a signal-to-noise ratio that exceeded all commercial two-photon systems tested. In addition to a detailed parts list, instructions for assembly, testing and troubleshooting, our plan includes complete three dimensional computer models that greatly reduce the knowledge base required for the non-expert user. This open-source resource lowers barriers in order to equip more laboratories with high-performance two-photon imaging and to help progress our understanding of the cellular and physiological function of living systems. 相似文献
998.
999.
A. J. Grant R. J. O'Connell 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2000,186(6):535-542
We recorded the electrophysiological responses of individual olfactory receptor neurons in sensilla trichodea on the antennae of adult arctiid moths, Utetheisa ornatrix, to stimulation with volatiles associated with both sexes. All trichoid sensilla contain at least two receptor neurons, each
with distinct action potential amplitudes and waveforms, that respond dichotomously to male and female odors. Although, neither
female neuron responds to extracts of coremata or the male-produced pheromone hydroxydanaidal, they do respond in a gender-specific
manner to the volatiles emanating from whole pupae, hemolymph, thoracic froth, and adult animals of several ages. Thoracic
froth, which contains pyrrolizidine alkaloids, is thought to play a role in defense. Froth from moths reared on diets, with
or without added pyrrolizidine alkaloids, were equally effective in eliciting gender-specific patterns of response. Male trichoid
receptor neurons respond to these same materials with similar patterns of activation. These receptor neurons provide information
about substances, which we have termed “gender odors,” that are persistently emitted by nearby animals. These substances do
not appear to be the same as those already known to be involved in defense or the sexual dialog between individuals.
Accepted: 16 March 2000 相似文献
1000.
By Martin A. Smith William A. Loneragan Carl D. Grant John M. Koch 《Ecological Management & Restoration》2000,1(1):50-60
Summary Germinable seed stores of 5- and 8-year-old rehabilitated bauxite mine pits in south-west Western Australia were assessed before and after burning. These seed stores were compared to those of adjacent unmined Jarrah ( Eucalyptus marginata ) forest, to identify at what age fire can be reintroduced, in order to measure restoration success and reduce fire hazard. Soils were sampled in early summer (before fire) and late autumn (after fire). Before fire, the mean topsoil seed bank of 5-year-old sites was 2121 seeds per m2 while 8-year-old sites had a mean of 1520 seeds per m2 . Only the 5-year-old sites were significantly different from the forest mean of 1478 seeds per m2 for the same season. After summer burns (and possibly due to seasonal effects) topsoil seed banks of rehabilitated areas (sampled in autumn) decreased by an average of 53 per cent. Topsoil seed banks of 5–8-year-old sites were resistant to lower intensity burns, with 362 seeds per m2 of native species surviving mild burns and 108 seeds per m2 of native species surviving after an intense summer fire. The topsoil seed reserve of 5–8-year-old rehabilitated areas had a high proportion of annual weed species while the forest sites had high levels of subshrubs and native annuals. Low-intensity burns did not alter the composition of life-forms in the soil seed bank, while intense burns favoured annual weed and shrub species. The results indicate that it is not appropriate to introduce fire to rehabilitated areas before 8 years, due to limited fuel reduction benefits and possible adverse effects on obligate seeding species. The large proportion of weed species in the soil seed bank of young rehabilitated areas is a concern, and remains a major consideration for future disturbance of these areas. 相似文献