全文获取类型
收费全文 | 8604篇 |
免费 | 1061篇 |
出版年
2021年 | 117篇 |
2019年 | 78篇 |
2018年 | 92篇 |
2017年 | 85篇 |
2016年 | 156篇 |
2015年 | 236篇 |
2014年 | 278篇 |
2013年 | 328篇 |
2012年 | 378篇 |
2011年 | 406篇 |
2010年 | 258篇 |
2009年 | 218篇 |
2008年 | 320篇 |
2007年 | 393篇 |
2006年 | 331篇 |
2005年 | 318篇 |
2004年 | 283篇 |
2003年 | 258篇 |
2002年 | 264篇 |
2001年 | 306篇 |
2000年 | 288篇 |
1999年 | 229篇 |
1998年 | 111篇 |
1997年 | 105篇 |
1996年 | 92篇 |
1995年 | 95篇 |
1994年 | 92篇 |
1993年 | 87篇 |
1992年 | 181篇 |
1991年 | 163篇 |
1990年 | 161篇 |
1989年 | 179篇 |
1988年 | 146篇 |
1987年 | 172篇 |
1986年 | 158篇 |
1985年 | 168篇 |
1984年 | 136篇 |
1983年 | 120篇 |
1982年 | 97篇 |
1981年 | 95篇 |
1980年 | 77篇 |
1979年 | 116篇 |
1978年 | 91篇 |
1977年 | 115篇 |
1976年 | 91篇 |
1974年 | 120篇 |
1973年 | 87篇 |
1972年 | 76篇 |
1971年 | 90篇 |
1969年 | 81篇 |
排序方式: 共有9665条查询结果,搜索用时 203 毫秒
991.
Moya M. Smith Zerina Johanson Thomas Butts Rolf Ericsson Melinda Modrell Frank J. Tulenko Marcus C. Davis Gareth J. Fraser 《Proceedings. Biological sciences / The Royal Society》2015,282(1805)
Ray-finned fishes (Actinopterygii) are the dominant vertebrate group today (+30 000 species, predominantly teleosts), with great morphological diversity, including their dentitions. How dental morphological variation evolved is best addressed by considering a range of taxa across actinopterygian phylogeny; here we examine the dentition of Polyodon spathula (American paddlefish), assigned to the basal group Acipenseriformes. Although teeth are present and functional in young individuals of Polyodon, they are completely absent in adults. Our current understanding of developmental genes operating in the dentition is primarily restricted to teleosts; we show that shh and bmp4, as highly conserved epithelial and mesenchymal genes for gnathostome tooth development, are similarly expressed at Polyodon tooth loci, thus extending this conserved developmental pattern within the Actinopterygii. These genes map spatio-temporal tooth initiation in Polyodon larvae and provide new data in both oral and pharyngeal tooth sites. Variation in cellular intensity of shh maps timing of tooth morphogenesis, revealing a second odontogenic wave as alternate sites within tooth rows, a dental pattern also present in more derived actinopterygians. Developmental timing for each tooth field in Polyodon follows a gradient, from rostral to caudal and ventral to dorsal, repeated during subsequent loss of teeth. The transitory Polyodon dentition is modified by cessation of tooth addition and loss. As such, Polyodon represents a basal actinopterygian model for the evolution of developmental novelty: initial conservation, followed by tooth loss, accommodating the adult trophic modification to filter-feeding. 相似文献
992.
Mala Isrie Martin Breuss Guoling Tian Andi?Harley Hansen Francesca Cristofoli Jasmin Morandell Zachari?A. Kupchinsky Alejandro Sifrim Celia?Maria Rodriguez-Rodriguez Elena?Porta Dapena Kurston Doonanco Norma Leonard Faten Tinsa Stéphanie Moortgat Hakan Ulucan Erkan Koparir Ender Karaca Nicholas Katsanis Valeria Marton Joris?Robert Vermeesch Erica?E. Davis Nicholas?J. Cowan David?Anthony Keays Hilde Van?Esch 《American journal of human genetics》2015,97(6):790-800
Circumferential skin creases Kunze type (CSC-KT) is a specific congenital entity with an unknown genetic cause. The disease phenotype comprises characteristic circumferential skin creases accompanied by intellectual disability, a cleft palate, short stature, and dysmorphic features. Here, we report that mutations in either MAPRE2 or TUBB underlie the genetic origin of this syndrome. MAPRE2 encodes a member of the microtubule end-binding family of proteins that bind to the guanosine triphosphate cap at growing microtubule plus ends, and TUBB encodes a β-tubulin isotype that is expressed abundantly in the developing brain. Functional analyses of the TUBB mutants show multiple defects in the chaperone-dependent tubulin heterodimer folding and assembly pathway that leads to a compromised yield of native heterodimers. The TUBB mutations also have an impact on microtubule dynamics. For MAPRE2, we show that the mutations result in enhanced MAPRE2 binding to microtubules, implying an increased dwell time at microtubule plus ends. Further, in vivo analysis of MAPRE2 mutations in a zebrafish model of craniofacial development shows that the variants most likely perturb the patterning of branchial arches, either through excessive activity (under a recessive paradigm) or through haploinsufficiency (dominant de novo paradigm). Taken together, our data add CSC-KT to the growing list of tubulinopathies and highlight how multiple inheritance paradigms can affect dosage-sensitive biological systems so as to result in the same clinical defect. 相似文献
993.
High cell density cultivation of Pseudomonas putida KT2440 using glucose without the need for oxygen enriched air supply 下载免费PDF全文
994.
David W. Frederick James G. Davis Antonio Dávila Jr. Beamon Agarwal Shaday Michan Michelle A. Puchowicz Eiko Nakamaru-Ogiso Joseph A. Baur 《The Journal of biological chemistry》2015,290(3):1546-1558
The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle. 相似文献
995.
Kelly A. Morris David B. Langston Donald W. Dickson Richard F. Davis Patricia Timper James P. Noe 《Journal of nematology》2015,47(4):310-315
Vegetable crops in the southeastern United States are commonly grown on plastic mulch with two crop cycles produced on a single mulch application. Field trials were conducted in 2013 and 2014 in two locations to evaluate the efficacy of fluensulfone for controlling Meloidogyne spp. when applied through drip irrigation to cucumber in a tomato–cucumber double-cropping system. In the spring tomato crop, 1,3-dichloropropene (1,3-D), fluensulfone, and a resistant cultivar significantly decreased root galling by 91%, 73%, and 97%, respectively, compared to the untreated control. Tomato plots from the spring were divided into split plots for the fall where the main plots were the spring treatment and the subplots were cucumber either treated with fluensulfone (3.0 kg a.i./ha. via drip irrigation) or left untreated. The fall application of fluensulfone improved cucumber vigor and reduced gall ratings compared to untreated subplots. Fluensulfone reduced damage from root-knot nematodes when applied to the first crop as well as provided additional protection to the second crop when it was applied through a drip system. 相似文献
996.
Confirmation of a wintering ground of Ross's Gull Rhodostethia rosea in the northern Labrador Sea 下载免费PDF全文
Ross's Gull Rhodostethia rosea is one of the world's least known seabirds; < 1% of the estimated global population can be accounted for at known breeding sites, and its wintering range has never been determined. Anecdotal reports over the last two centuries have prompted extensive speculation as to possible wintering areas used by this species in the north Pacific/Bering Sea region, but none has ever been confirmed. Using satellite and geolocator telemetry, we show that some Ross's Gulls from a colony in the Canadian Arctic winter in a restricted area of the northern Labrador Sea. Our discovery of a wintering area in the northwest Atlantic indicates that Ross's Gulls breeding in the Nearctic may be part of a disjunct population, or that birds breeding in the Palaearctic may winter off the east coast of North America. 相似文献
997.
998.
999.
Identification of P‐glycoprotein co‐fractionating proteins and specific binding partners in rat brain microvessels 下载免费PDF全文
Margaret E. Tome Charles P. Schaefer Leigh M. Jacobs Yifeng Zhang Joseph M. Herndon Fabian O. Matty Thomas P. Davis 《Journal of neurochemistry》2015,134(2):200-210
Drug delivery to the brain for the treatment of pathologies with a CNS component is a significant clinical challenge. P‐glycoprotein (PgP), a drug efflux pump in the endothelial cell membrane, is a major factor in preventing therapeutics from crossing the blood‐brain barrier (BBB). Identifying PgP regulatory mechanisms is key to developing agents to modulate PgP activity. Previously, we found that PgP trafficking was altered concomitant with increased PgP activity and disassembly of high molecular weight PgP‐containing complexes during acute peripheral inflammatory pain. These data suggest that PgP activity is post‐translationally regulated at the BBB. The goal of the current study was to identify proteins that co‐localize with PgP in rat brain microvessel endothelial cell membrane microdomains and use the data to suggest potential regulatory mechanisms. Using new density gradients of microvessel homogenates, we identified two unique pools (1,2) of PgP in membrane fractions. Caveolar constituents, caveolin1, cavin1, and cavin2, co‐localized with PgP in these fractions indicating the two pools contained caveolae. A chaperone (Hsc71), protein disulfide isomerase and endosomal/lysosomal sorting proteins (Rab5, Rab11a) also co‐fractionated with PgP in the gradients. These data suggest signaling pathways with a potential role in post‐translational regulation of PgP activity at the BBB.
1000.