全文获取类型
收费全文 | 9768篇 |
免费 | 1089篇 |
国内免费 | 1716篇 |
出版年
2024年 | 27篇 |
2023年 | 149篇 |
2022年 | 259篇 |
2021年 | 519篇 |
2020年 | 376篇 |
2019年 | 467篇 |
2018年 | 391篇 |
2017年 | 335篇 |
2016年 | 428篇 |
2015年 | 609篇 |
2014年 | 723篇 |
2013年 | 773篇 |
2012年 | 870篇 |
2011年 | 896篇 |
2010年 | 599篇 |
2009年 | 543篇 |
2008年 | 666篇 |
2007年 | 570篇 |
2006年 | 520篇 |
2005年 | 483篇 |
2004年 | 399篇 |
2003年 | 391篇 |
2002年 | 362篇 |
2001年 | 136篇 |
2000年 | 103篇 |
1999年 | 85篇 |
1998年 | 96篇 |
1997年 | 53篇 |
1996年 | 52篇 |
1995年 | 37篇 |
1994年 | 57篇 |
1993年 | 33篇 |
1992年 | 50篇 |
1991年 | 41篇 |
1990年 | 32篇 |
1989年 | 37篇 |
1988年 | 25篇 |
1987年 | 21篇 |
1986年 | 23篇 |
1985年 | 38篇 |
1984年 | 20篇 |
1983年 | 20篇 |
1982年 | 28篇 |
1981年 | 25篇 |
1980年 | 20篇 |
1979年 | 14篇 |
1978年 | 17篇 |
1976年 | 20篇 |
1975年 | 14篇 |
1974年 | 19篇 |
排序方式: 共有10000条查询结果,搜索用时 140 毫秒
991.
992.
Julie Earl Daniel Rico Enrique Carrillo-de-Santa-Pau Benjamín Rodríguez-Santiago Marinela Méndez-Pertuz Herbert Auer Gonzalo Gómez Herbert Barton Grossman David G Pisano Wolfgang A Schulz Luis A Pérez-Jurado Alfredo Carrato Dan Theodorescu Stephen Chanock Alfonso Valencia Francisco X Real 《BMC genomics》2015,16(1)
Background
Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression.Results
Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events.Conclusions
Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1450-3) contains supplementary material, which is available to authorized users. 相似文献993.
Silvas J Prince Li Song Dan Qiu Joao V Maldonado dos Santos Chenglin Chai Trupti Joshi Gunvant Patil Babu Valliyodan Tri D Vuong Mackensie Murphy Konstantinos Krampis Dominic M Tucker Ruslan Biyashev Anne E Dorrance MA Saghai Maroof Dong Xu J Grover Shannon Henry T Nguyen 《BMC genomics》2015,16(1)
Background
Root system architecture is important for water acquisition and nutrient acquisition for all crops. In soybean breeding programs, wild soybean alleles have been used successfully to enhance yield and seed composition traits, but have never been investigated to improve root system architecture. Therefore, in this study, high-density single-feature polymorphic markers and simple sequence repeats were used to map quantitative trait loci (QTLs) governing root system architecture in an inter-specific soybean mapping population developed from a cross between Glycine max and Glycine soja.Results
Wild and cultivated soybean both contributed alleles towards significant additive large effect QTLs on chromosome 6 and 7 for a longer total root length and root distribution, respectively. Epistatic effect QTLs were also identified for taproot length, average diameter, and root distribution. These root traits will influence the water and nutrient uptake in soybean. Two cell division-related genes (D type cyclin and auxin efflux carrier protein) with insertion/deletion variations might contribute to the shorter root phenotypes observed in G. soja compared with cultivated soybean. Based on the location of the QTLs and sequence information from a second G. soja accession, three genes (slow anion channel associated 1 like, Auxin responsive NEDD8-activating complex and peroxidase), each with a non-synonymous single nucleotide polymorphism mutation were identified, which may also contribute to changes in root architecture in the cultivated soybean. In addition, Apoptosis inhibitor 5-like on chromosome 7 and slow anion channel associated 1-like on chromosome 15 had epistatic interactions for taproot length QTLs in soybean.Conclusion
Rare alleles from a G. soja accession are expected to enhance our understanding of the genetic components involved in root architecture traits, and could be combined to improve root system and drought adaptation in soybean.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1334-6) contains supplementary material, which is available to authorized users. 相似文献994.
995.
Follicle‐stimulating hormone promotes age‐related endometrial atrophy through cross‐talk with transforming growth factor beta signal transduction pathway 下载免费PDF全文
Dan Zhang Jingyi Li Gufeng Xu Runjv Zhang Chengliang Zhou Yeqing Qian Yifeng Liu Luting Chen Bo Zhu Xiaoqun Ye Fan Qu Xinmei Liu Shuai Shi Weijun Yang Jianzhong Sheng Hefeng Huang 《Aging cell》2015,14(2):284-287
It is widely believed that endometrial atrophy in postmenopausal women is due to an age‐related reduction in estrogen level. But the role of high circulating follicle‐stimulating hormone (FSH) in postmenopausal syndrome is not clear. Here, we explored the role of high circulating FSH in physiological endometrial atrophy. We found that FSH exacerbated post‐OVX endometrial atrophy in mice, and this effect was ameliorated by lowering FSH with Gonadotrophin‐releasing hormone agonist (GnRHa). In vitro, FSH inhibited endometrial proliferation and promoted the apoptosis of primary cultured endometrial cells in a dose‐dependent manner. In addition, upregulation of caspase3, caspase8, caspase9, autophagy‐related proteins (ATG3, ATG5, ATG7, ATG12 and LC3) and downregulation of c‐Jun were also observed in endometrial adenocytes. Furthermore, smad2 and smad3 showed a time‐dependent activation in endometrial cells which can be partly inhibited by blocking the transforming growth factor beta receptor II (TβRII). In conclusion, FSH regulated endometrial atrophy by affecting the proliferation, autophagy and apoptosis of endometrial cells partly through activation of the transforming growth factor beta (TGFβ) pathway. 相似文献
996.
Dan Chen Satoko Ito Hong Yuan Toshinori Hyodo Kenji Kadomatsu Michinari Hamaguchi Takeshi Senga 《Cell cycle (Georgetown, Tex.)》2015,14(10):1529-1539
Echinoderm microtubule-associated protein (EMAP)-like (EML) family proteins are microtubule-associated proteins that have a conserved hydrophobic EMAP-like protein (HELP) domain and multiple WD40 domains. In this study, we examined the role of EML4, which is a member of the EML family, in cell division. Time-lapse microscopy analysis demonstrated that EML4 depletion induced chromosome misalignment during metaphase and delayed anaphase initiation. Further analysis by immunofluorescence showed that EML4 was required for the organization of the mitotic spindle and for the proper attachment of kinetochores to microtubules. We searched for EML4-associating proteins by mass spectrometry analysis and found that the nuclear distribution gene C (NUDC) protein, which is a critical factor for the progression of mitosis, was associated with EML4. This interaction was mediated by the WD40 repeat of EML4 and by the C-terminus of NUDC. In the absence of EML4, NUDC was no longer able to localize to the mitotic spindle, whereas NUDC was dispensable for EML4 localization. Our results show that EML4 is critical for the loading of NUDC onto the mitotic spindle for mitotic progression. 相似文献
997.
Hancock ML Nowakowski DW Role LW Talmage DA Flanagan JG 《Development (Cambridge, England)》2011,138(22):4887-4898
Sensory axons must develop appropriate connections with both central and peripheral targets. Whereas the peripheral cues have provided a classic model for neuron survival and guidance, less is known about the central cues or the coordination of central and peripheral connectivity. Here we find that type III Nrg1, in addition to its known effect on neuron survival, regulates axon pathfinding. In type III Nrg1(-/-) mice, death of TrkA(+) nociceptive/thermoreceptive neurons was increased, and could be rescued by Bax elimination. In the Bax and type III Nrg1 double mutants, axon pathfinding abnormalities were seen for TrkA(+) neurons both in cutaneous peripheral targets and in spinal cord central targets. Axon guidance phenotypes in the spinal cord included penetration of axons into ventral regions from which they would normally be repelled by Sema3A. Accordingly, sensory neurons from type III Nrg1(-/-) mice were unresponsive to the repellent effects of Sema3A in vitro, which might account, at least in part, for the central projection phenotype, and demonstrates an effect of type III Nrg1 on guidance cue responsiveness in neurons. Moreover, stimulation of type III Nrg1 back-signaling in cultured sensory neurons was found to regulate axonal levels of the Sema3A receptor neuropilin 1. These results reveal a molecular mechanism whereby type III Nrg1 signaling can regulate the responsiveness of neurons to a guidance cue, and show that type III Nrg1 is required for normal sensory neuron survival and axon pathfinding in both central and peripheral targets. 相似文献
998.
Yue Xiao Yu Zhang Bin Jiang Dan Dan Liu Yan Juan Niu Tian Gui 《World journal of microbiology & biotechnology》2011,27(9):2147-2153
A new alkaline keratinase, which could kill Meloidogyne incognita (a root-knot nematode) was separated and purified from Bacillus sp. 50-3 in this study. The solid ammonium sulfate was selected to precipitate the enzyme and its proper adding mass was
also determined. After solid ammonium sulfate precipitation and liquid chromatography on DEAE-Sephadex-A50 column, there was
17.7-fold purification with a yield of 46.5%, as determined by azokeratin as substrate. The purification effect was determined
through SDS-PAGE and the molecular weight of the enzyme was found to be 27,423 Da by the MALDI-TOF-MS. When the second-stage
juveniles of Meloidogyne incognita were exposed to 50 μg/ml of keratinase solution, 98.5% of Meloidogyne incognita mortality rates were obtained compared to control after 24 h. Its simple purification step and high yield from the cheap
medium affords this keratinase great biotechnological potential, especially in controlling root-knot nematodes such as Meloidogyne incognita. To the best of our knowledge, this study is the first report that uses keratinase as a pesticide. 相似文献
999.
Jin L Shang L Guo S Fang Y Wen D Wang L Yin J Dong S 《Biosensors & bioelectronics》2011,26(5):1965-1969
In this work, biomolecule-stabilized Au nanoclusters were demonstrated as a novel fluorescence probe for sensitive and selective detection of glucose. The fluorescence of Au nanoclusters was found to be quenched effectively by the enzymatically generated hydrogen peroxide (H(2)O(2)). By virtue of the specific response, the present assay allowed for the selective determination of glucose in the range of 1.0×10(-5) M to 0.5×10(-3) M with a detection limit of 5.0×10(-6) M. The absorption spectroscopy, X-ray photoelectron spectroscopy (XPS) and fluorescence decay studies were then performed to discuss the quenching mechanism. In addition, we demonstrated the application of the present approach in real serum samples, which suggested its great potential for diagnostic purposes. 相似文献
1000.
Acetylcholinesterase (AChE) activity is a well established biomarker for biomonitoring of exposures to organophosphates (OPs) pesticides and chemical nerve agents. In this work, we described a novel electrochemical oxidative desorption-process of thiocholine, the product of enzymatic reaction, for rapid and highly sensitive determination of AChE activity in human serum. This principle is based on self-assembling of produced thiocholine onto core-shell Fe(3)O(4)/Au nanoparticles (Fe(3)O(4)/AuNPs) magnetic nanocomposites and its oxidation at electrode surface. Fe(3)O(4) magnetic core is not only used for magnetic separation from sample solutions, but also carrying more AuNPs due to its large surface-to-volume ratio. The core-shell Fe(3)O(4)/AuNPs nanocomposites were characterized by UV-Vis spectroscopy, field-emission scanning electron microscopy (FE-SEM) and electrochemical measurements. A linear relationship was obtained between the AChE activity and its concentration from 0.05 to 5.0 mU mL(-1) with a detection limit of 0.02 mU mL(-1). The method showed good results for characterization of AChE spiked human serum and detection of OP exposures from 0.05 to 20 nM, with detection limit of 0.02 nM. This new oxidative desorption assay thus provides a sensitive and quantitative tool for biomonitoring of the exposure to OP pesticides and nerve agents. 相似文献