全文获取类型
收费全文 | 1272篇 |
免费 | 85篇 |
出版年
2023年 | 9篇 |
2022年 | 28篇 |
2021年 | 39篇 |
2020年 | 10篇 |
2019年 | 21篇 |
2018年 | 32篇 |
2017年 | 32篇 |
2016年 | 37篇 |
2015年 | 58篇 |
2014年 | 68篇 |
2013年 | 81篇 |
2012年 | 94篇 |
2011年 | 107篇 |
2010年 | 54篇 |
2009年 | 43篇 |
2008年 | 44篇 |
2007年 | 43篇 |
2006年 | 37篇 |
2005年 | 46篇 |
2004年 | 43篇 |
2003年 | 30篇 |
2002年 | 24篇 |
2001年 | 17篇 |
2000年 | 20篇 |
1999年 | 12篇 |
1995年 | 12篇 |
1994年 | 6篇 |
1992年 | 14篇 |
1991年 | 18篇 |
1990年 | 14篇 |
1989年 | 17篇 |
1988年 | 13篇 |
1987年 | 24篇 |
1986年 | 25篇 |
1985年 | 11篇 |
1984年 | 10篇 |
1982年 | 8篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 13篇 |
1978年 | 14篇 |
1977年 | 11篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1974年 | 11篇 |
1973年 | 12篇 |
1972年 | 6篇 |
1971年 | 5篇 |
1967年 | 5篇 |
1962年 | 5篇 |
排序方式: 共有1357条查询结果,搜索用时 15 毫秒
51.
Emmanuel S. Buys Yu-Chieh Ko Clemens Alt Sarah R. Hayton Alexander Jones Laurel T. Tainsh Ruiyi Ren Andrea Giani Maeva Clerté Emma Abernathy Robert E. T. Tainsh Dong-Jin Oh Rajeev Malhotra Pankaj Arora Nadine de Waard Binglan Yu Raphael Turcotte Daniel Nathan Marielle Scherrer-Crosbie Stephanie J. Loomis Jae H. Kang Charles P. Lin Haiyan Gong Douglas J. Rhee Peter Brouckaert Janey L. Wiggs Meredith S. Gregory Louis R. Pasquale Kenneth D. Bloch Bruce R. Ksander 《PloS one》2013,8(3)
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. 相似文献
52.
Vivek Malhotra 《The EMBO journal》2013,32(12):1660-1664
The process by which proteins are secreted without entering the classical endoplasmic reticulum (ER)–Golgi complex pathway, in eukaryotic cells, is conveniently called unconventional protein secretion. Recent studies on one such protein called Acb1 have revealed a number of components involved in its secretion. Interestingly, conditions that promote the secretion of Acb1 trigger the biogenesis of a new compartment called CUPS (Compartment for Unconventional Protein Secretion). CUPS form near the ER exit site but lack ER‐specific proteins. Other proteins that share some of the features common with the secretion of Acb1 are interleukin‐1β and tissue transglutaminase. Here I will review recent advances made in the field and propose a new model for unconventional protein secretion. 相似文献
53.
54.
Gordonia are high GC gram-positive bacteria that have not yet been exploited well for biotechnological purposes because of the limited genetic tools. Described here is an improved protocol for electroporation, which is useful for several Gordonia species. The maximum transformation efficiency obtained was 2.8 × 104/μg (Gordonia rubropertinctus, Gordonia sp), and 1.7 × 103/μg (Gordonia amarae). 相似文献
55.
Kalyani Prasad Pooja Bhatnagar-Mathur Farid Waliyar Kiran K. Sharma 《Journal of plant biochemistry and biotechnology.》2013,22(2):222-233
A chitinase gene from rice (Rchit) was introduced into three varieties of peanut through Agrobacterium-mediated genetic transformation resulting in 30 transgenic events harboring the Rchit gene. Stable integration and expression of the transgenes were confirmed using PCR, RT-PCR and Southern blot analysis. Progeny derived from selfing of the primary transgenic events revealed a Mendelian inheritance pattern (3:1) for the transgenes. The chitinase activity in the leaves of the transgenic events was 2 to 14-fold greater than that in the non-transformed control plants. Seeds of most transgenic events showed 0–10 % A. flavus infection during in vitro seed inoculation bioassays. Transgenic peanut plants evaluated for resistance against late leaf spot (LLS) and rust using detached leaf assays showed longer incubation, latent period and lower infection frequencies when compared to their non-transformed counterparts. A significant negative correlation existed between the chitinase activity and the frequency of infection to the three tested pathogens. Three progenies from two transgenic events displayed significantly higher disease resistance for LLS, rust and A. flavus infection and are being advanced for further evaluations under confined field conditions to confirm as sources to develop peanut varieties with enhanced resistance to these fungal pathogens. 相似文献
56.
Pooja Dhupkar Huang Zhao Kalpana Mujoo Zhiqiang An Ningyan Zhang 《Biochemistry and Biophysics Reports》2016
Crk (C10 regulator of kinase) adaptor proteins are highly expressed in many types of human cancers and often contribute to aggressive cancer phenotypes. Crk II, a member of CRK family, has been reported to regulate cell migration and metastasis in breast cancer cells. However, its role in other cancer types has not been reported. In this study, we investigated the molecular function of Crk II in prostate cancer (PCa) cells (CWR-22rv1) in vitro and using a mouse tumor model. Results showed that Crk II knockdown by shRNA-mediated silencing (Crk II-shRNA) in the PCa cells significantly inhibited both cancer cell migration and invasion in cell culture study. Crk II-shRNA cancer cells also significantly decreased colony formation in vitro, but had no significant reduction of tumor volume after 4 weeks of cancer cell xenografting in vivo when compared to the scramble control. Interestingly, Crk II-shRNA cancer cells showed a greatly reduced level of insulin-like growth factor 1 receptor (IGF-1R) and decreased signaling of the IGF-1R/PI3K/Akt axis upon IGF-1 ligand stimulation. A close interaction between Crk II and IGF-1R was demonstrated upon co-immunoprecipitation of IGF-1R with Crk II protein. Further, treatment of cells with either proteosomal degradation or protein synthesis inhibitor showed higher proportion of ubiquitin-associated IGF-1R and faster degradation of IGF-1R in Crk II-shRNA cells in comparison with that in the control cancer cells. Taken together, these data suggest that Crk II plays an important role in the regulation of IGF-1R protein stability and affects downstream of IGF-1R signaling pathways. Therefore, targeting Crk-II can block IGF-1R growth signaling and suppress cancer cell invasion and progression. 相似文献
57.
Vijya Rabari Purvi Rakhashiya Pooja Patel Vrinda Thaker 《Journal of Phytopathology》2016,164(4):286-289
A leaf spot disease was observed on Mangifera indica L. located in the region of Rajkot, Gujarat, India. The symptoms included the appearance of small, circular to oval dark brown necrotic sunken spots on the leaves. The fungus formed grey to dark grey on potato dextrose agar and conidia were single‐celled, ovoid or oblong. On the basis of mycological characteristics, pathogenicity test and molecular identification using 28S rDNA sequence and internal transcribed spacer (ITS), the fungus was identified as Botryosphaeria dothidea. To the best of our knowledge, this is the first report of leaf spot on M. indica tree caused by Botryoshaeria dothidea in Gujarat, India. 相似文献
58.
Zafar Rukhsar Chauhan Pooja Salim Mohammad Singh Ghanshyam 《Plasmonics (Norwell, Mass.)》2019,14(4):1013-1017
Plasmonics - Photonics provides a key solution to limit the myriads of challenges offered by existing silicon technology. Here, we propose a simple 2-channel Plasmonic demultiplexer with... 相似文献
59.
Kanika Narula Pooja Choudhary Sudip Ghosh Eman Elagamey Niranjan Chakraborty Subhra Chakraborty 《Proteomics》2019,19(3)
Modulation of plant immune system by extrinsic/intrinsic factors and host‐specific determinants fine‐tunes cellular components involving multiple organelles, particularly nucleus to mount resistance against pathogen attack. Rice blast, caused by hemibiotrophic fungus Magnaporthe oryzae, is one of the most devastating diseases that adversely affect rice productivity. However, the role of nuclear proteins and their regulation in response to M. oryzae remains unknown. Here, the nucleus‐associated immune pathways in blast‐resistant rice genotype are elucidated. Temporal analysis of nuclear proteome is carried out using 2‐DE coupled MS/MS analysis. A total of 140 immune responsive proteins are identified associated with nuclear reorganization, cell division, energy production/deprivation, signaling, and gene regulation. The proteome data are interrogated using correlation network analysis that identified significant functional modules pointing toward immune‐related coinciding processes through a common mechanism of remodeling and homeostasis. Novel clues regarding blast resistance include nucleus‐associated redox homeostasis and glycolytic enzyme–mediated chromatin organization which manipulates cell division and immunity. Taken together, the study herein provides evidence that the coordination of nuclear function and reprogramming of host translational machinery regulate resistance mechanism against blast disease. 相似文献
60.
Anil Chekuri Katarzyna Zientara‐Rytter Angel Soto‐Hermida Shyamanga Borooah Marina Voronchikhina Pooja Biswas Virender Kumar David Goodsell Caroline Hayward Peter Shaw Chloe Stanton Donita Garland Suresh Subramani Radha Ayyagari 《Aging cell》2019,18(6)
Late‐onset retinal degeneration (L‐ORD) is an autosomal dominant macular degeneration characterized by the formation of sub‐retinal pigment epithelium (RPE) deposits and neuroretinal atrophy. L‐ORD results from mutations in the C1q‐tumor necrosis factor‐5 protein (CTRP5), encoded by the CTRP5/C1QTNF5 gene. To understand the mechanism underlying L‐ORD pathology, we used a human cDNA library yeast two‐hybrid screen to identify interacting partners of CTRP5. Additionally, we analyzed the Bruch's membrane/choroid (BM‐Ch) from wild‐type (Wt), heterozygous S163R Ctrp5 mutation knock‐in (Ctrp5S163R/wt), and homozygous knock‐in (Ctrp5S163R/S163R) mice using mass spectrometry. Both approaches showed an association between CTRP5 and HTRA1 via its C‐terminal PDZ‐binding motif, stimulation of the HTRA1 protease activity by CTRP5, and CTRP5 serving as an HTRA1 substrate. The S163R‐CTRP5 protein also binds to HTRA1 but is resistant to HTRA1‐mediated cleavage. Immunohistochemistry and proteomic analysis showed significant accumulation of CTRP5 and HTRA1 in BM‐Ch of Ctrp5S163R/S163R and Ctrp5S163R/wt mice compared with Wt. Additional extracellular matrix (ECM) components that are HTRA1 substrates also accumulated in these mice. These results implicate HTRA1 and its interaction with CTRP5 in L‐ORD pathology. 相似文献