全文获取类型
收费全文 | 1868篇 |
免费 | 173篇 |
专业分类
2041篇 |
出版年
2024年 | 4篇 |
2023年 | 20篇 |
2022年 | 41篇 |
2021年 | 55篇 |
2020年 | 32篇 |
2019年 | 64篇 |
2018年 | 68篇 |
2017年 | 68篇 |
2016年 | 70篇 |
2015年 | 126篇 |
2014年 | 114篇 |
2013年 | 130篇 |
2012年 | 187篇 |
2011年 | 149篇 |
2010年 | 104篇 |
2009年 | 79篇 |
2008年 | 95篇 |
2007年 | 78篇 |
2006年 | 75篇 |
2005年 | 75篇 |
2004年 | 79篇 |
2003年 | 58篇 |
2002年 | 68篇 |
2001年 | 23篇 |
2000年 | 12篇 |
1999年 | 12篇 |
1998年 | 9篇 |
1997年 | 7篇 |
1996年 | 6篇 |
1995年 | 6篇 |
1994年 | 3篇 |
1993年 | 12篇 |
1992年 | 9篇 |
1991年 | 8篇 |
1990年 | 6篇 |
1989年 | 12篇 |
1988年 | 6篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 6篇 |
1984年 | 4篇 |
1983年 | 5篇 |
1982年 | 6篇 |
1980年 | 4篇 |
1979年 | 3篇 |
1977年 | 6篇 |
1975年 | 5篇 |
1973年 | 7篇 |
1970年 | 2篇 |
1969年 | 2篇 |
排序方式: 共有2041条查询结果,搜索用时 0 毫秒
121.
Linlin Wang Sujeethraj Koppolu Catherine Chappell Bernard J. Moncla Sharon L. Hillier Lara K. Mahal 《PloS one》2015,10(5)
The cervicovaginal fluid (CVF) coating the vaginal epithelium is an important immunological mediator, providing a barrier to infection. Glycosylation of CVF proteins, such as mucins, IgG and S-IgA, plays a critical role in their immunological functions. Although multiple factors, such as hormones and microflora, may influence glycosylation of the CVF, few studies have examined their impact on this important immunological fluid. Herein we analyzed the glycosylation of cervicovaginal lavage (CVL) samples collected from 165 women under different hormonal conditions including: (1) no contraceptive, post-menopausal, (2) no contraceptive, days 1-14 of the menstrual cycle, (3) no contraceptive, days 15-28 of the menstrual cycle, (4) combined-oral contraceptive pills for at least 6 months, (5) depo-medroxyprogesterone acetate (Depo-Provera) injections for at least 6 months, (6) levonorgestrel IUD for at least 1 month. Glycomic profiling was obtained using our lectin microarray system, a rapid method to analyze carbohydrate composition. Although some small effects were observed due to hormone levels, the major influence on the glycome was the presence of an altered bacterial cohort due to bacterial vaginosis (BV). Compared to normal women, samples from women with BV contained lower levels of sialic acid and high-mannose glycans in their CVL. The change in high mannose levels was unexpected and may be related to the increased risk of HIV-infection observed in women with BV, as high mannose receptors are a viral entry pathway. Changes in the glycome were also observed with hormonal contraceptive use, in a contraceptive-dependent manner. Overall, microflora had a greater impact on the glycome than hormonal levels, and both of these effects should be more closely examined in future studies given the importance of glycans in the innate immune system. 相似文献
122.
Mesenchymal stem cell (MSC) therapy is the most clinically advanced form of cell therapy, second to hematopoietic stem cell transplants. To date, MSC have been used for immune modulation in conditions such as Graft Versus Host Disease (GVHD) and Crohn's Disease, for which Phase III clinical trials are currently in progress. Here, we review the immunological properties of MSC and make a case for their use in treatment of Charcot-Marie-Tooth disease type 1 (CMT1), a group of inherited peripheral neuropathies. CMT1 is characterized by demyelination and aberrant immune activation making this condition an ideal target for exploration of MSC therapy, given the ability of these cells to promote sheath regeneration as well as suppress inflammation. Studies supporting this hypothesis will be presented and placed into the context of other cell-based approaches that are theoretically feasible. Given that MSCs selectively home to areas of inflammation, as well as exert effects in an allogeneic manner, the possibility of an "off the shelf" therapy for CMT1 will be discussed. 相似文献
123.
Neuropeptide Y-like immunoreactivity was studied in the thalamus of the cat using an indirect immunoperoxidase method. The densest network of immunoreactive fibers was observed in the nucleus (n.) paraventricularis anterior. In the anterior, intralaminar and midline thalamic nuclei, as well as in the n. geniculatum medialis, n. geniculatum lateralis, n. habenularis lateralis, n. medialis dorsalis, n. lateralis posterior and n. pulvinar a low density of neuropeptide Y-like immunoreactive fibers was observed. Neuropeptide Y-like fibers were totally absent in the n. ventralis lateralis, n. ventralis medialis, n. ventralis postero-medialis and n. ventralis postero-lateralis. In addition, neuropeptide Y-like perikarya were found in the n. parafascicularis, n. suprageniculatus, n. geniculatum lateralis ventralis, n. medialis dorsalis and n. lateralis posterior. 相似文献
124.
Occurrence of 16SrIV Subgroup A Phytoplasmas in Roystonea regia and Acrocomia mexicana Palms with Lethal Yellowing‐like Syndromes in Yucatán,Mexico
下载免费PDF全文
![点击此处可从《Journal of Phytopathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
María Narvaez Iván Córdova‐Lara Celso Reyes‐Martínez Carlos Puch‐Hau Luis Mota‐Narvaez Ana Collí Goretti Caamal Nigel Harrison Luis Sáenz Carlos Oropeza 《Journal of Phytopathology》2016,164(11-12):1111-1115
The lethal yellowing (LY) disease and LY‐type syndromes affecting several palm species are associated with 16SrIV phytoplasmas in the Americas. In Mexico, palms of the species Roystonea regia and the native Acrocomia mexicana were found to exhibit LY‐type symptoms, including leaf decay, starting with mature leaves, necrosis and atrophy of inflorescences. DNA extracts obtained from these palms could be amplified by nested‐PCR using phytoplasma‐universal primer pair P1/P7 followed by LY‐group‐specific primer pair LY16Sr/LY16Sf. Blast analysis of the sequences obtained revealed an identity of 100% for R. regia and 99.27% for A. mexicana with 16SrIV‐A strain associated with LY in Florida, USA (Acc. AF498309 ). Computer‐simulated RFLP analysis showed that the patterns for the phytoplasma DNA of the two palm species were highly similar to that for 16SrIV subgroup A strain. A neighbour‐joining tree was constructed, and the sequences of the two palm species clustered in the same clade of group 16SrIV subgroup A. The results therefore support that LY‐type syndromes observed in palms of R. regia and A. mexicana in the Yucatan region of Mexico are associated with 16SrIV subgroup A phytoplasmas. 相似文献
125.
Lee KS Raymond LD Schoen B Raymond GJ Kett L Moore RA Johnson LM Taubner L Speare JO Onwubiko HA Baron GS Caughey WS Caughey B 《The Journal of biological chemistry》2007,282(50):36525-36533
Hemin (iron protoporphyrin IX) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. Some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (PrPC). These observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for PrPC. Accordingly, we evaluated PrPC interactions with hemin. When hemin (3-10 microM) was added to the medium of cultured cells, clusters of PrPC formed on the cell surface, and the detergent solubility of PrPC decreased. The addition of hemin also induced PrPC internalization and turnover. The ability of hemin to bind directly to PrPC was demonstrated by hemin-agarose affinity chromatography and UV-visible spectroscopy. Multiple hemin molecules bound primarily to the N-terminal third of PrPC, with reduced binding to PrPC lacking residues 34-94. These hemin-PrPC interactions suggest that PrPC may participate in hemin homeostasis, sensing, and/or uptake and that hemin might affect PrPC functions. 相似文献
126.
127.
Lara A. Underkoffler Erikka Carr Anthony Nelson Matthew J. Ryan Reiner Schultz Kathleen M. Loomes 《PloS one》2013,8(12)
Alagille syndrome is an autosomal dominant disorder involving bile duct paucity and cholestasis in addition to cardiac, skeletal, ophthalmologic, renal and vascular manifestations. Mutations in JAG1, encoding a ligand in the Notch signaling pathway, are found in 95% of patients meeting clinical criteria for Alagille syndrome. In order to define the role of Jag1 in the bile duct developmental abnormalities seen in ALGS, we previously created a Jag1 conditional knockout mouse model. Mice heterozygous for the Jag1 conditional and null alleles demonstrate abnormalities in postnatal bile duct growth and remodeling, with portal expansion and increased numbers of malformed bile ducts. In this study we report the results of microarray analysis and identify genes and pathways differentially expressed in the Jag1 conditional/null livers as compared with littermate controls. In the initial microarray analysis, we found that many of the genes up-regulated in the Jag1 conditional/null mutant livers were related to extracellular matrix (ECM) interactions, cell adhesion and cell migration. One of the most highly up-regulated genes was Ddr1, encoding a receptor tyrosine kinase (RTK) belonging to a large RTK family. We have found extensive co-localization of Jag1 and Ddr1 in bile ducts and blood vessels in postnatal liver. In addition, co-immunoprecipitation data provide evidence for a novel protein interaction between Jag1 and Ddr1. Further studies will be required to define the nature of this interaction and its functional consequences, which may have significant implications for bile duct remodeling and repair of liver injury. 相似文献
128.
Aim It is well established that many groups of plants and animals have undergone long-distance dispersal, but the extent to which this continues beyond initial colonization is largely unknown. To provide further insight into the frequency of gene flow mediated by long-distance dispersal, we investigated the origins of the fern Asplenium hookerianum on the Chatham Islands, and present a review of the contribution of molecular data to elucidating the origins of this archipelago's biota.
Location Chatham Islands and New Zealand. A. hookerianum is scarce on the Chatham Islands but common in New Zealand, some 800 km to the west.
Methods We compared chloroplast trnL–trnF DNA sequence data from Chatham Islands' A. hookerianum with extensive phylogeographic data for this genetically variable species in mainland New Zealand.
Results Our sequencing revealed the presence of two haplotypes in Chatham Islands' A. hookerianum . These haplotypes differed by four mutational events and were each more closely related to haplotypes found in New Zealand than to each other.
Main conclusions Despite the rarity of A. hookerianum on the Chatham Islands, its populations there appear to derive from at least two long-distance dispersal events from New Zealand, these possibly originating from different areas. We suggest that long-distance transoceanic dispersal, and the gene flow it can mediate, may be more common than is generally appreciated. 相似文献
Location Chatham Islands and New Zealand. A. hookerianum is scarce on the Chatham Islands but common in New Zealand, some 800 km to the west.
Methods We compared chloroplast trnL–trnF DNA sequence data from Chatham Islands' A. hookerianum with extensive phylogeographic data for this genetically variable species in mainland New Zealand.
Results Our sequencing revealed the presence of two haplotypes in Chatham Islands' A. hookerianum . These haplotypes differed by four mutational events and were each more closely related to haplotypes found in New Zealand than to each other.
Main conclusions Despite the rarity of A. hookerianum on the Chatham Islands, its populations there appear to derive from at least two long-distance dispersal events from New Zealand, these possibly originating from different areas. We suggest that long-distance transoceanic dispersal, and the gene flow it can mediate, may be more common than is generally appreciated. 相似文献
129.
Lara J. Wolfson Anna Walker Robert Hettle Xiaoyan Lu Chrispin Kambili Andrew Murungi Gerhart Knerer 《PloS one》2015,10(3)
Objective
To evaluate the cost-effectiveness of adding bedaquiline to a background regimen (BR) of drugs for multidrug-resistant tuberculosis (MDR-TB) in the United Kingdom (UK).Methods
A cohort-based Markov model was developed to estimate the incremental cost-effectiveness ratio of bedaquiline plus BR (BBR) versus BR alone (BR) in the treatment of MDR-TB, over a 10-year time horizon. A National Health Service (NHS) and personal social services perspective was considered. Cost-effectiveness was evaluated in terms of Quality-Adjusted Life Years (QALYs) and Disability-Adjusted Life Years (DALYs). Data were sourced from a phase II, placebo-controlled trial, NHS reference costs, and the literature; the US list price of bedaquiline was used and converted to pounds (£18,800). Costs and effectiveness were discounted at a rate of 3.5% per annum. Probabilistic and deterministic sensitivity analysis was conducted.Results
The total discounted cost per patient (pp) on BBR was £106,487, compared with £117,922 for BR. The total discounted QALYs pp were 5.16 for BBR and 4.01 for BR. The addition of bedaquiline to a BR resulted in a cost-saving of £11,434 and an additional 1.14 QALYs pp over a 10-year period, and is therefore considered to be the dominant (less costly and more effective) strategy over BR. BBR remained dominant in the majority of sensitivity analyses, with a 81% probability of being dominant versus BR in the probabilistic analysis.Conclusions
In the UK, bedaquiline is likely to be cost-effective and cost-saving, compared with the current MDR-TB standard of care under a range of scenarios. Cost-savings over a 10-year period were realized from reductions in length of hospitalization, which offset the bedaquiline drug costs. The cost-benefit conclusions held after several sensitivity analyses, thus validating assumptions made, and suggesting that the results would hold even if the actual price of bedaquiline in the UK were higher than in the US. 相似文献130.
Maria Teresa Lara Ortiz Pablo Benjamín Leon Rosario Pablo Luna-Nevarez Alba Savin Gamez Ana Martínez-del Campo Gabriel Del Rio 《PloS one》2015,10(2)
Relating a gene mutation to a phenotype is a common task in different disciplines such as protein biochemistry. In this endeavour, it is common to find false relationships arising from mutations introduced by cells that may be depurated using a phenotypic assay; yet, such phenotypic assays may introduce additional false relationships arising from experimental errors. Here we introduce the use of high-throughput DNA sequencers and statistical analysis aimed to identify incorrect DNA sequence-phenotype assignments and observed that 10–20% of these false assignments are expected in large screenings aimed to identify critical residues for protein function. We further show that this level of incorrect DNA sequence-phenotype assignments may significantly alter our understanding about the structure-function relationship of proteins. We have made available an implementation of our method at http://bis.ifc.unam.mx/en/software/chispas. 相似文献