全文获取类型
收费全文 | 2316篇 |
免费 | 144篇 |
国内免费 | 3篇 |
出版年
2023年 | 16篇 |
2022年 | 21篇 |
2021年 | 37篇 |
2020年 | 30篇 |
2019年 | 32篇 |
2018年 | 39篇 |
2017年 | 30篇 |
2016年 | 80篇 |
2015年 | 113篇 |
2014年 | 140篇 |
2013年 | 162篇 |
2012年 | 193篇 |
2011年 | 209篇 |
2010年 | 108篇 |
2009年 | 103篇 |
2008年 | 143篇 |
2007年 | 152篇 |
2006年 | 132篇 |
2005年 | 127篇 |
2004年 | 77篇 |
2003年 | 111篇 |
2002年 | 83篇 |
2001年 | 7篇 |
2000年 | 8篇 |
1998年 | 20篇 |
1997年 | 18篇 |
1996年 | 10篇 |
1995年 | 10篇 |
1994年 | 8篇 |
1993年 | 18篇 |
1992年 | 14篇 |
1991年 | 10篇 |
1990年 | 12篇 |
1989年 | 12篇 |
1988年 | 12篇 |
1987年 | 12篇 |
1986年 | 12篇 |
1985年 | 10篇 |
1984年 | 9篇 |
1983年 | 12篇 |
1982年 | 12篇 |
1981年 | 6篇 |
1980年 | 10篇 |
1979年 | 17篇 |
1978年 | 11篇 |
1977年 | 6篇 |
1975年 | 6篇 |
1972年 | 5篇 |
1971年 | 5篇 |
1969年 | 6篇 |
排序方式: 共有2463条查询结果,搜索用时 15 毫秒
71.
This study delineates the role of peroxiredoxin 3 (Prx3) in hair cell death induced by several etiologies of acquired hearing loss (noise trauma, aminoglycoside treatment, age). In vivo, Prx3 transiently increased in mouse cochlear hair cells after traumatic noise exposure, kanamycin treatment, or with progressing age before any cell loss occurred; when Prx3 declined, hair cell loss began. Maintenance of high Prx3 levels via treatment with the radical scavenger 2,3-dihydroxybenzoate prevented kanamycin-induced hair cell death. Conversely, reducing Prx3 levels with Prx3 siRNA increased the severity of noise-induced trauma. In mouse organ of Corti explants, reactive oxygen species and levels of Prx3 mRNA and protein increased concomitantly at early times of drug challenge. When Prx3 levels declined after prolonged treatment, hair cells began to die. The radical scavenger p-phenylenediamine maintained Prx3 levels and attenuated gentamicin-induced hair cell death. Our results suggest that Prx3 is up-regulated in response to oxidative stress and that maintenance of Prx3 levels in hair cells is a critical factor in their susceptibility to acquired hearing loss. 相似文献
72.
73.
Bertram Geinitz Lars Rehmann Jochen Büchs Lars Regestein 《Biotechnology and bioengineering》2020,117(4):999-1011
Cocultures bear great potential in the conversion of complex substrates and process intensification, as well as, in the formation of unique components only available due to inter-species interactions. Dynamic data of coculture composition is necessary for understanding and optimizing coculture systems. However, most standard online determined parameters measure the sum of all species in the reactor system. The kinetic behavior of the individual species remains unknown. Up to now, different offline methods are available to determine the culture composition, as well as the online measurement of fluorescence of genetically modified organisms. To avoid any genetic modification, a noninvasive online monitoring tool based on the scattered light spectrum was developed for microtiter plate cultivations. To demonstrate the potential, a coculture consisting of the bacterium Lactococcus lactis and the yeast Kluyveromyces marxianus was cultivated. Via partial least squares regression of scattered light spectra, the online determination of the individual biomass concentrations without further sampling and analyses is possible. The results were successfully validated by a Coulter counter-analysis, taking advantage of the different cell sizes of both organisms. The findings prove the applicability of the new method to follow in detail the dynamics of a coculture. 相似文献
74.
Norbert Pfeiffer Julia Lamparter Adrian Gericke Franz H. Grus Esther M. Hoffmann Jochen Wahl 《Cell and tissue research》2013,353(2):245-251
Intraocular pressure (IOP)-lowering therapy has been shown to arrest or retard the progression of optic neuropathy typical for glaucoma and can, thus, be described as neuroprotective. At present, six classes of medical therapy are employed, namely parasympathomimetics, alpha/beta-sympathomimetics, β-blockers, carbonic anhydrase inhibitors, α2-adrenergic receptor agonists and prostaglandin analogues. For several of these substances, some experimental evidence exists of a possible neuroprotective mechanism, beyond their IOP-lowering activity. β-Blockers are involved in the up-regulation of brain-derived neurotrophic factor (BDNF) and can decrease glutamate-mediated NMDA receptor activation. Not only systemic but also topical carbonic anhydrase inhibitors are able to increase retinal blood flow. α2-Adrenergic receptor agonists can up-regulate the formation of BDNF and anti-apoptotic factors. Prostaglandin analogues increase blood flow to the eye, possibly including the retina. To date, evidence for a neuroprotective effect independent of IOP regulation in human glaucoma is scarce and has only been shown to be likely for the α2-adrenergic receptor agonist, brimonidine. 相似文献
75.
Marie Dacke Marcus Byrne Jochen Smolka Eric Warrant Emily Baird 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2013,199(1):17-23
Upon locating a suitable dung pile, ball-rolling dung beetles shape a piece of dung into a ball and roll it away in a straight line. This guarantees that they will not return to the dung pile, where they risk having their ball stolen by other beetles. Dung beetles are known to use celestial compass cues such as the sun, the moon and the pattern of polarised light formed around these light sources to roll their balls of dung along straight paths. Here, we investigate whether terrestrial landmarks have any influence on straight-line orientation in dung beetles. We find that the removal or re-arrangement of landmarks has no effect on the beetle’s orientation precision. Celestial compass cues dominate straight-line orientation in dung beetles so strongly that, under heavily overcast conditions or when prevented from seeing the sky, the beetles can no longer orient along straight paths. To our knowledge, this is the only animal with a visual compass system that ignores the extra orientation precision that landmarks can offer. 相似文献
76.
Biodiversity can provide insurance against environmental change, but only if species differ in their response to environmental conditions (response diversity). Wild bees provide pollination services to wild and crop plants, and response diversity might insure this function against changing climate. To experimentally test the hypothesis that bee species differ in their response to increasing winter temperature, we stored cocoons of nine bee species at different temperatures during the winter (1.5–9.5 °C). Bee species differed significantly in their responses (weight loss, weight at emergence and emergence date). The developmental stage during the winter explained some of these differences. Bee species overwintering as adults generally showed decreased weight and earlier emergence with increasing temperature, whereas bee species overwintering in pre-imaginal stages showed weaker or even opposite responses. This means that winter warming will likely affect some bee species negatively by increasing energy expenditure, while others are less sensitive presumably due to different physiology. Likewise, species phenologies will respond differently to winter warming, potentially affecting plant–pollinator interactions. Responses are not independent of current flight periods: bees active in spring will likely show the strongest phenological advances. Taken together, wild bee diversity provides response diversity to climate change, which may be the basis for an insurance effect. 相似文献
77.
78.
Julia M. Eckl Daniel A. Rutz Veronika Haslbeck Bettina K. Zierer Jochen Reinstein Klaus Richter 《The Journal of biological chemistry》2013,288(22):16032-16042
The ATPase-driven dimeric molecular Hsp90 (heat shock protein 90) and its cofactor Cdc37 (cell division cycle 37 protein) are crucial to prevent the cellular depletion of many protein kinases. In complex with Hsp90, Cdc37 is thought to bind an important lid structure in the ATPase domain of Hsp90 and inhibit ATP turnover by Hsp90. As different interaction modes have been reported, we were interested in the interaction mechanism of Hsp90 and Cdc37. We find that Cdc37 can bind to one subunit of the Hsp90 dimer. The inhibition of the ATPase activity is caused by a reduction in the closing rate of Hsp90 without obviously bridging the two subunits or affecting nucleotide accessibility to the binding site. Although human Cdc37 binds to the N-terminal domain of Hsp90, nematodal Cdc37 preferentially interacts with the middle domain of CeHsp90 and hHsp90, exposing two Cdc37 interaction sites. A previously unreported site in CeCdc37 is utilized for the middle domain interaction. Dephosphorylation of CeCdc37 by the Hsp90-associated phosphatase PPH-5, a step required during the kinase activation process, proceeds normally, even if only the new interaction site is used. This shows that the second interaction site is also functionally relevant and highlights that Cdc37, similar to the Hsp90 cofactors Sti1 and Aha1, may utilize two different attachment sites to restrict the conformational freedom and the ATP turnover of Hsp90. 相似文献
79.
Andreas D. Kistler Geetika Singh Mehmet M. Altintas Hao Yu Isabel C. Fernandez Changkyu Gu Cory Wilson Sandeep Kumar Srivastava Alexander Dietrich Katherina Walz Dontscho Kerjaschki Phillip Ruiz Stuart Dryer Sanja Sever Amit K. Dinda Christian Faul Jochen Reiser 《The Journal of biological chemistry》2013,288(51):36598-36609
Gain-of-function mutations in the calcium channel TRPC6 lead to autosomal dominant focal segmental glomerulosclerosis and podocyte expression of TRPC6 is increased in some acquired human glomerular diseases, particularly in membranous nephropathy. These observations led to the hypothesis that TRPC6 overactivation is deleterious to podocytes through pathological calcium signaling, both in genetic and acquired diseases. Here, we show that the effects of TRPC6 on podocyte function are context-dependent. Overexpression of TRPC6 alone did not directly affect podocyte morphology and cytoskeletal structure. Unexpectedly, however, overexpression of TRPC6 protected podocytes from complement-mediated injury, whereas genetic or pharmacological TRPC6 inactivation increased podocyte susceptibility to complement. Mechanistically, this effect was mediated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation. Podocyte-specific TRPC6 transgenic mice showed stronger CaMKII activation, reduced podocyte foot process effacement and reduced levels of proteinuria during nephrotoxic serum nephritis, whereas TRPC6 null mice exhibited reduced CaMKII activation and higher levels of proteinuria compared with wild type littermates. Human membranous nephropathy biopsy samples showed podocyte staining for active CaMKII, which correlated with the degree of TRPC6 expression. Together, these data suggest a dual and context dependent role of TRPC6 in podocytes where acute activation protects from complement-mediated damage, but chronic overactivation leads to focal segmental glomerulosclerosis. 相似文献
80.
Daniel Wibberg Jochen Blom Christian Rückert Anika Winkler Andreas Albersmeier Alfred Pühler Andreas Schlüter Birgit E. Scharf 《Journal of biotechnology》2013
Sinorhizobium meliloti of the order Rhizobiales is a symbiotic nitrogen-fixing bacterium nodulating plants of the genera Medicago, Trigonella and Melilotus and hence is of great agricultural importance. In its free-living state it is motile and capable of modulating its movement patterns in response to chemical attractants. Here, the draft genome consisting of a circular chromosome, the megaplasmids pSymA and pSymB and three accessory plasmids of Sinorhizobium meliloti RU11/001, a model organism for flagellum structure, motility and chemotaxis, is reported. 相似文献