全文获取类型
收费全文 | 4388篇 |
免费 | 323篇 |
国内免费 | 2篇 |
出版年
2023年 | 17篇 |
2022年 | 32篇 |
2021年 | 61篇 |
2020年 | 43篇 |
2019年 | 66篇 |
2018年 | 75篇 |
2017年 | 61篇 |
2016年 | 94篇 |
2015年 | 190篇 |
2014年 | 202篇 |
2013年 | 251篇 |
2012年 | 358篇 |
2011年 | 378篇 |
2010年 | 247篇 |
2009年 | 215篇 |
2008年 | 305篇 |
2007年 | 294篇 |
2006年 | 243篇 |
2005年 | 265篇 |
2004年 | 236篇 |
2003年 | 235篇 |
2002年 | 236篇 |
2001年 | 65篇 |
2000年 | 42篇 |
1999年 | 52篇 |
1998年 | 48篇 |
1997年 | 33篇 |
1996年 | 24篇 |
1995年 | 31篇 |
1994年 | 29篇 |
1993年 | 22篇 |
1992年 | 25篇 |
1991年 | 27篇 |
1990年 | 24篇 |
1989年 | 14篇 |
1988年 | 13篇 |
1987年 | 15篇 |
1986年 | 7篇 |
1985年 | 7篇 |
1984年 | 13篇 |
1983年 | 16篇 |
1982年 | 13篇 |
1981年 | 11篇 |
1980年 | 10篇 |
1979年 | 5篇 |
1978年 | 11篇 |
1977年 | 9篇 |
1976年 | 10篇 |
1975年 | 7篇 |
1974年 | 7篇 |
排序方式: 共有4713条查询结果,搜索用时 281 毫秒
91.
Eucalyptus nitens is an important forestry species grown for pulp and paper production in the temperate, summer-rainfall regions of South Africa. A tree improvement programme has been ongoing at the Institute for Commercial Forestry Research for two decades, but genetic improvement in the species has been slow due to delayed and infrequent flowering and seed production. Three trials were established, firstly, to quantify the gains that have been made in the first generation of improvement in the breeding programme and, secondly, to establish whether a number of seed source and orchard variables influence the performance of the progeny. These variables were the amount of flowering trees in the seed orchard, year of seed collection, seed orchard origin and composition of seed orchard bulks. Diameter at breast height and tree heights were measured in the trials at between 87 and 97 months after establishment, and timber volumes and survival were calculated. Improved seed orchard bulks performed significantly better (p?<?0.01) than unimproved controls in the field trials. Genetic gains ranging from 23.2 to 164.8 m3?ha?1 were observed over the unimproved commercial seed. There were significant differences (p?<?0.01) in progeny growth between the levels of seed orchard flowering, with higher levels of flowering (≥40 %) producing substantially greater progeny growth than lower flowering levels (≤20 %). The seed orchard had no effect on progeny growth in this trial series. This suggests that seed collected from any of the four seed orchards tested will produce trees with significant improvement in growth. 相似文献
92.
93.
Stanley M. Walls Jr Steve J. Attle Gregory B. Brulte Marlena L. Walls Kim D. Finley Dale A. Chatfield Deron R. Herr Greg L. Harris 《PLoS genetics》2013,9(12)
Obesity is defined by excessive lipid accumulation. However, the active mechanistic roles that lipids play in its progression are not understood. Accumulation of ceramide, the metabolic hub of sphingolipid metabolism, has been associated with metabolic syndrome and obesity in humans and model systems. Here, we use Drosophila genetic manipulations to cause accumulation or depletion of ceramide and sphingosine-1-phosphate (S1P) intermediates. Sphingolipidomic profiles were characterized across mutants for various sphingolipid metabolic genes using liquid chromatography electrospray ionization tandem mass spectroscopy. Biochemical assays and microscopy were used to assess classic hallmarks of obesity including elevated fat stores, increased body weight, resistance to starvation induced death, increased adiposity, and fat cell hypertrophy. Multiple behavioral assays were used to assess appetite, caloric intake, meal size and meal frequency. Additionally, we utilized DNA microarrays to profile differential gene expression between these flies, which mapped to changes in lipid metabolic pathways. Our results show that accumulation of ceramides is sufficient to induce obesity phenotypes by two distinct mechanisms: 1) Dihydroceramide (C14:0) and ceramide diene (C14:2) accumulation lowered fat store mobilization by reducing adipokinetic hormone- producing cell functionality and 2) Modulating the S1P: ceramide (C14:1) ratio suppressed postprandial satiety via the hindgut-specific neuropeptide like receptor dNepYr, resulting in caloric intake-dependent obesity. 相似文献
94.
Yu S. Zhou Sheila Webb Laura Lettice Steve Tardif Fiona Kilanowski Christine Tyrrell Heather MacPherson Fiona Semple Peter Tennant Tina Baker Alan Hart Paul Devenney Paul Perry Tracey Davey Perdita Barran Chris L. Barratt Julia R. Dorin 《PLoS genetics》2013,9(10)
β-defensin peptides are a family of antimicrobial peptides present at mucosal surfaces, with the main site of expression under normal conditions in the male reproductive tract. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. We show here that homozygous deletion of a cluster of nine β-defensin genes (DefbΔ9) in the mouse results in male sterility. The sperm derived from the mutants have reduced motility and increased fragility. Epididymal sperm isolated from the cauda should require capacitation to induce the acrosome reaction but sperm from the mutants demonstrate precocious capacitation and increased spontaneous acrosome reaction compared to wild-types but have reduced ability to bind the zona pellucida of oocytes. Ultrastructural examination reveals a defect in microtubule structure of the axoneme with increased disintegration in mutant derived sperm present in the epididymis cauda region, but not in caput region or testes. Consistent with premature acrosome reaction, sperm from mutant animals have significantly increased intracellular calcium content. Thus we demonstrate in vivo that β-defensins are essential for successful sperm maturation, and their disruption leads to alteration in intracellular calcium, inappropriate spontaneous acrosome reaction and profound male infertility. 相似文献
95.
Katherine R. Bull Andrew J. Rimmer Owen M. Siggs Lisa A. Miosge Carla M. Roots Anselm Enders Edward M. Bertram Tanya L. Crockford Belinda Whittle Paul K. Potter Michelle M. Simon Ann-Marie Mallon Steve D. M. Brown Bruce Beutler Christopher C. Goodnow Gerton Lunter Richard J. Cornall 《PLoS genetics》2013,9(1)
Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis. 相似文献
96.
97.
Candy Kumps Annelies Fieuw Pieter Mestdagh Bj?rn Menten Steve Lefever Filip Pattyn Sara De Brouwer Tom Sante Johannes Hubertus Schulte Alexander Schramm Nadine Van Roy Tom Van Maerken Rosa Noguera Valérie Combaret Christine Devalck Frank Westermann Geneviève Laureys Angelika Eggert Jo Vandesompele Katleen De Preter Frank Speleman 《PloS one》2013,8(1)
Neuroblastoma is an embryonic tumor arising from immature sympathetic nervous system cells. Recurrent genomic alterations include MYCN and ALK amplification as well as recurrent patterns of gains and losses of whole or large partial chromosome segments. A recent whole genome sequencing effort yielded no frequently recurring mutations in genes other than those affecting ALK. However, the study further stresses the importance of DNA copy number alterations in this disease, in particular for genes implicated in neuritogenesis. Here we provide additional evidence for the importance of focal DNA copy number gains and losses, which are predominantly observed in MYCN amplified tumors. A focal 5 kb gain encompassing the MYCN regulated miR-17∼92 cluster as sole gene was detected in a neuroblastoma cell line and further analyses of the array CGH data set demonstrated enrichment for other MYCN target genes in focal gains and amplifications. Next we applied an integrated genomics analysis to prioritize MYCN down regulated genes mediated by MYCN driven miRNAs within regions of focal heterozygous or homozygous deletion. We identified RGS5, a negative regulator of G-protein signaling implicated in vascular normalization, invasion and metastasis, targeted by a focal homozygous deletion, as a new MYCN target gene, down regulated through MYCN activated miRNAs. In addition, we expand the miR-17∼92 regulatory network controlling TGFß signaling in neuroblastoma with the ring finger protein 11 encoding gene RNF11, which was previously shown to be targeted by the miR-17∼92 member miR-19b. Taken together, our data indicate that focal DNA copy number imbalances in neuroblastoma (1) target genes that are implicated in MYCN signaling, possibly selected to reinforce MYCN oncogene addiction and (2) serve as a resource for identifying new molecular targets for treatment. 相似文献
98.
Emily R. Winter Andrew M. Hindes Steve Lane J. Robert Britton 《Journal of fish biology》2020,97(4):1209-1219
Biotelemetry is a central tool for fisheries management, with the implantation of transmitters into animals requiring refined surgical techniques that maximize retention rates and fish welfare. Even following successful surgery, long-term post-release survival rates can vary considerably, although knowledge is limited for many species. The aim here was to investigate the post-tagging survival rates in the wild of two lowland river fish species, common bream Abramis brama and northern pike Esox lucius, following their intra-peritoneal double-tagging with acoustic transmitters and passive integrated transponder (PIT) tags. Survival over a 2-year period was assessed using acoustic transmitter data in Cox proportional hazards models. Post-tagging survival rates were lowest in the reproductive periods of both species, but in bream, fish tagged just prior to spawning actually had the highest subsequent survival rates. Pike survival was influenced by sex, with males generally surviving longer than females. PIT tag detections at fixed stations identified bream that remained active, despite loss of an acoustic transmitter signal. In these instances, loss of the acoustic signal occurred up to 215 days post-tagging and only during late spring or summer, indicating a role of elevated temperature, while PIT detections occurred between 18 and 359 days after the final acoustic detections. Biotelemetry studies must thus always consider the date of tagging as a fundamental component of study designs to avoid tagged fish having premature end points within telemetry studies. 相似文献
99.
Lie Maria E. K. Kickinger Stefanie Skovgaard-Petersen Jonas Ecker Gerhard F. Clausen Rasmus P. Schousboe Arne White H. Steve Wellendorph Petrine 《Neurochemical research》2020,45(7):1551-1565
Neurochemical Research - Focal epileptic seizures can in some patients be managed by inhibiting γ-aminobutyric acid (GABA) uptake via the GABA transporter 1 (GAT1) using tiagabine... 相似文献
100.
The actinobacterial transcription factor RbpA binds to the principal sigma subunit of RNA polymerase