全文获取类型
收费全文 | 1918篇 |
免费 | 134篇 |
专业分类
2052篇 |
出版年
2024年 | 1篇 |
2023年 | 6篇 |
2022年 | 22篇 |
2021年 | 28篇 |
2020年 | 23篇 |
2019年 | 49篇 |
2018年 | 45篇 |
2017年 | 42篇 |
2016年 | 73篇 |
2015年 | 109篇 |
2014年 | 110篇 |
2013年 | 143篇 |
2012年 | 166篇 |
2011年 | 139篇 |
2010年 | 95篇 |
2009年 | 93篇 |
2008年 | 126篇 |
2007年 | 123篇 |
2006年 | 102篇 |
2005年 | 101篇 |
2004年 | 97篇 |
2003年 | 77篇 |
2002年 | 75篇 |
2001年 | 14篇 |
2000年 | 9篇 |
1999年 | 9篇 |
1998年 | 20篇 |
1997年 | 22篇 |
1996年 | 18篇 |
1995年 | 19篇 |
1994年 | 18篇 |
1993年 | 16篇 |
1992年 | 13篇 |
1991年 | 10篇 |
1990年 | 9篇 |
1989年 | 5篇 |
1988年 | 7篇 |
1987年 | 3篇 |
1986年 | 6篇 |
1985年 | 1篇 |
1984年 | 2篇 |
1983年 | 2篇 |
1982年 | 2篇 |
1980年 | 2篇 |
排序方式: 共有2052条查询结果,搜索用时 15 毫秒
71.
72.
A microdeletion of less than 250 kb, including the proximal part of the FMR-1 gene and the fragile-X site, in a male with the clinical phenotype of fragile-X syndrome 下载免费PDF全文
Doris Whrle Dieter Kotzot Mark C. Hirst Antonella Manca Bernhard Korn Angela Schmidt Gotthold Barbi Hans-Dieter Rott Annemarie Poustka Kay E. Davies Peter Steinbach 《American journal of human genetics》1992,51(2):299-306
A gene designated "FMR-1" has been isolated at the fragile-X locus. One exon of this gene is carried on a 5.1-kb EcoRI fragment that exhibits length variation in fragile-X patients because of amplification of or insertion into a CGG-repeat sequence. This repeat probably represents the fragile site. The EcoRI fragment also includes an HTF island that is hypermethylated in fragile-X patients showing absence of FMR-1 mRNA. In this paper, we present further evidence that the FMR-1 gene is involved in the clinical manifestation of the fragile-X syndrome and also in the expression of the cellular phenotype. A deletion including the HTF island and exons of the FMR-1 gene was detected in a fragile X-negative mentally retarded male who presented the clinical phenotype of the fragile-X syndrome. The deletion involves less than 250 kb of genomic DNA, including DXS548 and at least five exons of the FMR-1 gene. These data support the hypothesis that loss of function of the FMR-1 gene leads to the clinical phenotype of the fragile-X syndrome. In the fragile-X syndrome, there are pathogenetic mechanisms other than amplification of the CGG repeat that do have the same phenotypic consequences. 相似文献
73.
To investigate the role of satellite DNA in eukaryotic genomes, we isolated from an African green monkey (Cercopithecus aethiops) genomic library cloned segments containing the previously described deca-satellite linked to low-copy-number genomic sequences. Three such clones were obtained. The low-copy-number sequences in the three clones do not cross-hybridize suggesting that they derive from different genomic loci. The structure of one of the clones, λAMkA, is described in detail. Subcloned segments containing the low-copy-number sequences from λAMkA anneal to monkey, human and mouse genomic DNA. The subcloned probes were used to select clones containing homologous sequences from a second, independent monkey library as well as from human and mouse genomic libraries. Several of the newly isolated monkey clones hybridized to probes containing the species-specific deca- and -satellites, confirming the genomic association of the low-copy-number sequence in λAMkA with satellite DNA. Moreover, several of the human and mouse clones hybridized to species-specific human and mouse satellite DNAs, respectively. These experiments indicate that the low-copy-number sequence in λMkA and its association with satellite DNA is conserved in primates and rodents. 相似文献
74.
Giulia Borgonovo Eleonora Paulicelli Deborah Daniele Stefano Presilla Antonella Richetti Mariacarla Valli 《Reports of Practical Oncology and Radiotherapy》2022,27(4):717
BackgroundThe aim of our study is to determine whether deep inspiration breath hold (DIBH) is effective for reducing exposure of the heart, left coronary artery (LAD) and both lungs in right breast radiotherapy.Materials and methodsWe have analyzed 10 consecutive patients with right-sided breast cancer (BC), simulated during free breathing (FB) and in DIBH modality. For all patients we contoured breast PTV and organs at risk (right and left lungs, heart, LAD) on both CT scans (FB and DIBH). Finally, 5 patients were treated with IMRT and 5 with VMAT techniques.ResultsAll patients were able to end the treatments in DIBH modalities regardless of the longer treatment time in comparison to FB. The maximum and mean dose to the heart are lower in the DIBH modality. The mean values of the heart mean dose were 1.76 Gy in DIBH and 2.19 Gy in FB. The mean heart maximum dose in DIBH and FB were, respectively, 9.3 Gy and 11 Gy. Likewise, the maximum dose to the LAD is lower in DIBH; 2.57 Gy versus 3.56 Gy in FB. Noteworthy, 3 patients with hepatomegaly treated with the DIBH technique showed a higher ipsilateral lung dose than FB, but a decrease of liver dose.ConclusionWe report that the use of DIBH for right-sided BC allows the dose to the heart, LAD and to the liver to be reduced in case of hepatomegaly. This technique is well tolerated by patients, when adequately trained, and could be considered effective even in right sided BC. 相似文献
75.
76.
Wild Sicilian Rosemary: Phytochemical and Morphological Screening and Antioxidant Activity Evaluation of Extracts and Essential Oils 下载免费PDF全文
Edoardo M. Napoli Laura Siracusa Antonella Saija Antonio Speciale Domenico Trombetta Teresa Tuttolomondo Salvatore La Bella Mario Licata Giuseppe Virga Raffaele Leone Claudio Leto Laura Rubino Giuseppe Ruberto 《化学与生物多样性》2015,12(7):1075-1094
To identify the best biotypes, an extensive survey of Sicilian wild rosemary was carried out by collecting 57 samples from various sites, followed by taxonomic characterization from an agronomic perspective. All the biotypes collected were classified as Rosmarinus officinalis L. A cluster analysis based on the morphological characteristics of the plants allowed the division of the biotypes into seven main groups, although the characteristics examined were found to be highly similar and not area‐dependent. Moreover, all samples were analyzed for their phytochemical content, applying an extraction protocol to obtain the nonvolatile components and hydrodistillation to collect the essential oils for the volatile components. The extracts were characterized by LC‐UV‐DAD/ESI‐MS, and the essential oils by GC‐FID and GC/MS analyses. In the nonvolatile fractions, 18 components were identified, namely, 13 flavones, two organic acids, and three diterpenes. In the volatile fractions, a total of 82 components were found, with as predominant components α‐pinene and camphene among the monoterpene hydrocarbons and 1,8‐cineole, camphor, borneol, and verbenone among the oxygenated monoterpenes. Cluster analyses were carried out on both phytochemical profiles, allowing the separation of the rosemary samples into different chemical groups. Finally, the total phenol content and the antioxidant activity of the essential oils and extracts were determined with the Folin–Ciocalteu (FC) colorimetric assay, the UV radiation‐induced peroxidation in liposomal membranes (UV‐IP test), and the scavenging activity of the superoxide radical (O$\rm{{_{2}^{{^\cdot} -}}}$ ). The present study confirmed that the essential oils and organic extracts of the Sicilian rosemary samples analyzed showed a considerable antioxidant/free radical‐scavenging activity. 相似文献
77.
Gianmauro Numico Antonella Cristofano Alessandro Mozzicafreddo Olga Elisabetta Cursio Pierfrancesco Franco Giulia Courthod Antonio Trogu Alessandra Malossi Mariella Cucchi Zuzana Sirotovà Maria Rosa Alvaro Anna Stella Fulvia Grasso Silvia Spinazzé Nicola Silvestris 《PloS one》2015,10(3)
Background
Cancer patients are frequently admitted to hospital due to acute conditions or refractory symptoms. This occurs through the emergency departments and requires medical oncologists to take an active role. The use of acute-care hospital increases in the last months of life.Patients and methods
We aimed to describe the admissions to a medical oncology inpatient service within a 16-month period with respect to patients and tumor characteristics, and the outcome of the hospital stay.Results
672 admissions of 454 patients were analysed. The majority of admissions were urgent (74.1%), and were due to uncontrolled symptoms (79.6%). Among the chief complaints, dyspnoea occurred in 15.7%, pain in 15.2%, and neurological symptoms in 14.5%. The majority of the hospitalizations resulted in discharge to home (60.6%); in 26.5% the patient died and in 11.0% was transferred to a hospice. Admissions due to symptoms correlated with a longer hospital stay and a higher incidence of in-hospital death.Conclusion
We suggest that hospital use is not necessarily a sign of inappropriately aggressive care: inpatient care is probably an unavoidable step in the cancer trajectory. Optimization of inpatient supportive procedures should be a specific task of modern medical oncology. 相似文献78.
Aaron M. Dickey Vivek Kumar J. Kent Morgan Antonella Jara-Cavieres Robert G. Shatters Jr. Cindy L. McKenzie Lance S. Osborne 《BMC genomics》2015,16(1)
Background
Multipartite mitochondrial genomes are very rare in animals but have been found previously in two insect orders with highly rearranged genomes, the Phthiraptera (parasitic lice), and the Psocoptera (booklice/barklice).Results
We provide the first report of a multipartite mitochondrial genome architecture in a third order with highly rearranged genomes: Thysanoptera (thrips). We sequenced the complete mitochondrial genomes of two divergent members of the Scirtothrips dorsalis cryptic species complex. The East Asia 1 species has the single circular chromosome common to animals while the South Asia 1 species has a genome consisting of two circular chromosomes. The fragmented South Asia 1 genome exhibits extreme chromosome size asymmetry with the majority of genes on the large, 14.28 kb, chromosome and only nad6 and trnC on the 0.92 kb mini-circle chromosome. This genome also features paralogous control regions with high similarity suggesting a very recent origin of the nad6 mini-circle chromosome in the South Asia 1 cryptic species.Conclusions
Thysanoptera, along with the other minor paraenopteran insect orders should be considered models for rapid mitochondrial genome evolution, including fragmentation. Continued use of these models will facilitate a greater understanding of recombination and other mitochondrial genome evolutionary processes across eukaryotes.Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1672-4) contains supplementary material, which is available to authorized users. 相似文献79.
Microbial lipase from Candida rugosa was immobilized by physical adsorption onto an ethylene-vinyl alcohol polymer (EVAL) functionalized with acyl chlorides. To evaluate the influence of the reagent chain-length on the amount and activity of immobilized lipase, three differently long aliphatic fatty acids were employed (C8, C12, C18), obtaining EVAL functionalization degrees ranging from 5% to 65%. The enzyme-polymer affinity increased with both the length of the alkyl chain and the matrix hydrophobicity. In particular, the esterified polymers showed a tendency to give segregated hydrophilic and hydrophobic domains. It was observed the formation of an enzyme multilayer at both low and high protein concentrations. Desorption experiments showed that Candida rugosa lipase may be adsorbed in a closed form on the polymer hydrophilic domains and in an open, active structure on the hydrophobic ones. The best results were found for the EVAL-C18 13% matrix that showed hyperactivation with both the soluble and unsoluble substrate after enzyme desorption. In addition, this supported biocatalyst retained its activity for repetitive cycles. 相似文献
80.
Mattia Criscuoli Cristina Ulivieri Irene Filippi Sara Monaci Giuditta Guerrini Bianca Crifò Domiziana De Tommaso Giuliana Pelicci Cosima T. Baldari Cormac T. Taylor Fabio Carraro Antonella Naldini 《Journal of cellular physiology》2020,235(11):8058-8070
Hypoxia occurs in physiological and pathological conditions. T cells experience hypoxia in pathological and physiological conditions as well as in lymphoid organs. Indeed, hypoxia-inducible factor 1α (HIF-1α) affects T cell survival and functions. Rai, an Shc family protein member, exerts pro-survival effects in hypoxic neuroblastoma cells. Since Rai is also expressed in T cells, we here investigated its role in hypoxic T cells. In this work, hypoxia differently affected cell survival, proapoptotic, and metabolic programs in T cells, depending upon Rai expression. By using Jurkat cells stably expressing Rai and splenocytes from Rai−/−mice, we demonstrated that Rai promotes T cell survival and affects cell metabolism under hypoxia. Upon exposure to hypoxia, Jurkat T cells expressing Rai show (a) higher HIF-1α protein levels; (b) a decreased cell death and increased Akt/extracellular-signal-regulated kinase phosphorylation; (c) a decreased expression of proapoptotic markers, including caspase activities and poly(ADP-ribose) polymerase cleavage; (d) an increased glucose and lactate metabolism; (e) an increased activation of nuclear factor-kB pathway. The opposite effects were observed in hypoxic splenocytes from Rai−/−mice. Thus, Rai plays an important role in hypoxic signaling and may be relevant in the protection of T cells against hypoxia. 相似文献