全文获取类型
收费全文 | 433篇 |
免费 | 45篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 4篇 |
儿科学 | 12篇 |
妇产科学 | 10篇 |
基础医学 | 68篇 |
口腔科学 | 14篇 |
临床医学 | 46篇 |
内科学 | 75篇 |
皮肤病学 | 7篇 |
神经病学 | 13篇 |
特种医学 | 27篇 |
外科学 | 62篇 |
综合类 | 5篇 |
预防医学 | 39篇 |
眼科学 | 17篇 |
药学 | 35篇 |
肿瘤学 | 45篇 |
出版年
2022年 | 12篇 |
2021年 | 20篇 |
2020年 | 8篇 |
2019年 | 15篇 |
2018年 | 17篇 |
2017年 | 11篇 |
2016年 | 12篇 |
2015年 | 14篇 |
2014年 | 17篇 |
2013年 | 31篇 |
2012年 | 24篇 |
2011年 | 29篇 |
2010年 | 15篇 |
2009年 | 22篇 |
2008年 | 17篇 |
2007年 | 36篇 |
2006年 | 18篇 |
2005年 | 14篇 |
2004年 | 26篇 |
2003年 | 19篇 |
2002年 | 20篇 |
2001年 | 6篇 |
2000年 | 8篇 |
1999年 | 8篇 |
1998年 | 4篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 2篇 |
1994年 | 2篇 |
1993年 | 2篇 |
1992年 | 4篇 |
1991年 | 3篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1986年 | 3篇 |
1984年 | 2篇 |
1980年 | 1篇 |
1979年 | 3篇 |
1978年 | 2篇 |
1977年 | 1篇 |
1976年 | 1篇 |
1975年 | 2篇 |
1974年 | 1篇 |
1973年 | 2篇 |
1972年 | 1篇 |
1970年 | 1篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1961年 | 1篇 |
1929年 | 1篇 |
排序方式: 共有479条查询结果,搜索用时 15 毫秒
81.
Roger A. Renne Hiroyuki Yoshimura Kei Yoshino George Lulham Susumu Minamisawa Albrecht Tribukait 《Inhalation toxicology》2013,25(9):685-706
A series of in vitro and in vivo studies evaluated the potential effects of tobacco flavoring and casing ingredients. Study 1 utilized as a reference control cigarette a typical commercial tobacco blend without flavoring ingredients, and a test cigarette containing a mixture of 165 low-use flavoring ingredients. Study 2 utilized the same reference control cigarette as used in study 1 and a test cigarette containing eight high-use ingredients. The in vitro Ames Salmonella typhimurium assay did not show any increase in mutagenicity of smoke condensate from test cigarettes designed for studies 1 and 2 as compared to the reference. Sprague-Dawley rats were exposed by nose-only inhalation for 1 h/day, 5 days/wk for 13 wk to smoke from the test or reference cigarettes already described, or to air only, and necropsied after 13 wk of exposure or following 13 wk of recovery from smoke exposure. Exposure to smoke from reference or test cigarettes in both studies induced increases in blood carboxyhemoglobin ((COHb)) and plasma nicotine, decreases in minute volume, differences in body or organ weights compared to air controls, and a concentration-related hyperplasia, squamous metaplasia, and inflammation in the respiratory tract. All these effects were greatly decreased or absent following the recovery period. Comparison of rats exposed to similar concentrations of test and reference cigarette smoke indicated no difference at any concentration. In summary, the results did not indicate any consistent differences in toxicologic effects between smoke from cigarettes containing the flavoring or casing ingredients and reference cigarettes. 相似文献
82.
Ruli Gao Chunxia Cao Min Zhang Maria-Cecilia Lopez Yuanqing Yan Zirong Chen Yoshitsugu Mitani Li Zhang Maria Zajac-Kaye Bin Liu Lizi Wu Rolf Renne Henry V. Baker Adel El-Naggar Frederic J. Kaye 《Oncotarget》2014,5(24):12528-12542
MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target. 相似文献
83.
Khayat M Korman SH Frankel P Weintraub Z Hershckowitz S Sheffer VF Ben Elisha M Wevers RA Falik-Zaccai TC 《Molecular genetics and metabolism》2008,94(4):431-434
The rare autosomal recessive disorder pyridoxine 5′-phosphate oxidase (PNPO) deficiency is a recently described cause of neonatal and infantile seizures. Clinical evaluation, and biochemical and genetic testing, were performed on a neonate with intractable seizures who did not respond to anticonvulsant drugs and pyridoxine. Sequencing of the PNPO gene revealed a novel homozygous c.284G>A transition in exon 3, resulting in arginine to histidine substitution and reduced activity of the PNPO mutant to 18% relative to the wild type. This finding enabled molecular prenatal diagnosis in a subsequent pregnancy, accurate genetic counseling in the large inbred family, and population screening. 相似文献
84.
Stevens EL Heckenberg G Baugher JD Roberson ED Downey TJ Pevsner J 《European journal of human genetics : EJHG》2012,20(6):657-667
A set of Centre d'étude du Polymorphisme Humain (CEPH) cell lines serves as a large reference collection that has been widely used as a benchmark for allele frequencies in the analysis of genetic variants, to create linkage maps of the human genome, to study the genetics of gene expression, to provide samples to the HapMap and 1000 Genomes projects, and for a variety of other applications. An explicit feature of the CEPH collection is that these multigenerational families represent reference panels of known relatedness, consisting mostly of three-generation pedigrees with large sibships, two parents, and grandparents. We applied identity-by-state (IBS) and identity-by-descent (IBD) methods to high-density genotype data from 186 CEPH individuals in 13 families. We identified unexpected relatedness between nominally unrelated grandparents both within and between pedigrees. For one pair, the estimated Cotterman coefficient of relatedness k1 exceeded 0.2, consistent with one-eighth sharing (eg, first-cousins). Unexpectedly, significant IBD2 values were discovered in both second-degree and parent-child relationships. These were accompanied by regions of homozygosity in the offspring, which corresponded to blocks lacking IBS0 in purportedly unrelated parents, consistent with inbreeding. Our findings support and extend a 1999 report, based on the use of short tandem-repeat polymorphisms, that several CEPH families had regions of homozygosity consistent with autozygosity. We benchmarked our IBD approach (called kcoeff) against both RELPAIR and PREST software packages. Our findings may affect the interpretation of previous studies and the design of future studies that rely on the CEPH resource. 相似文献
85.
ED Mackey SE Engle MR Kim HC O'Neill CR Wageman NE Patzlaff Y Wang SR Grady JM McIntosh MJ Marks HA Lester RM Drenan 《The Journal of neuroscience》2012,32(30):10226-10237
Nicotinic acetylcholine receptors (nAChRs) containing α6 subunits are expressed in only a few brain areas, including midbrain dopamine (DA) neurons, noradrenergic neurons of the locus ceruleus, and retinal ganglion cells. To better understand the regional and subcellular expression pattern of α6-containing nAChRs, we created and studied transgenic mice expressing a variant α6 subunit with green fluorescent protein (GFP) fused in-frame in the M3-M4 intracellular loop. In α6-GFP transgenic mice, α6-dependent synaptosomal DA release and radioligand binding experiments confirmed correct expression and function in vivo. In addition to strong α6* nAChR expression in glutamatergic retinal axons, which terminate in superficial superior colliculus (sSC), we also found α6 subunit expression in a subset of GABAergic cell bodies in this brain area. In patch-clamp recordings from sSC neurons in brain slices from mice expressing hypersensitive α6* nAChRs, we confirmed functional, postsynaptic α6* nAChR expression. Further, sSC GABAergic neurons expressing α6* nAChRs exhibit a tonic conductance mediated by standing activation of hypersensitive α6* nAChRs by ACh. α6* nAChRs also appear in a subpopulation of SC neurons in output layers. Finally, selective activation of α6* nAChRs in vivo induced sSC neuronal activation as measured with c-Fos expression. Together, these results demonstrate that α6* nAChRs are uniquely situated to mediate cholinergic modulation of glutamate and GABA release in SC. The SC has emerged as a potential key brain area responsible for transmitting short-latency salience signals to thalamus and midbrain DA neurons, and these results suggest that α6* nAChRs may be important for nicotinic cholinergic sensitization of this pathway. 相似文献
86.
Johnson Courtney A. Tran Dan N. Mwangi Ann Sosa-Rub Sandra G. Chivardi Carlos Romero-Martnez Martn Pastakia Sonak Robinson Elisha Jennings Mayo-Wilson Larissa Galrraga Omar 《Health services & outcomes research methodology》2022,22(3):297-316
Health Services and Outcomes Research Methodology - To slow the spread of COVID-19, most countries implemented stay-at-home orders, social distancing, and other nonpharmaceutical mitigation... 相似文献
87.
William W. Tseng Denice D. Tsao-Wei Dario Callegaro Giovanni Grignani Lorenzo DAmbrosio Sylvie Bonvalot Cecilia G. Ethun Kenneth Cardona John T. Mullen Robert J. Canter John E. Mullinax Ricardo J. Gonzalez Frits van Coevorden Markus Albertsmeier Kiran K. Dhanireddy Salvatore L. Renne Alessandro Gronchi 《European journal of surgical oncology》2018,44(6):810-815
Background
In retroperitoneal sarcoma (RPS), the optimal extent of resection must balance adequate disease control with potential for morbidity. We sought to study the frequency and outcomes after a Whipple procedure or pancreaticoduodenectomy (PD) in patients undergoing resection for primary RPS.Methods
Participating referral centers within the Trans-Atlantic Retroperitoneal Sarcoma Working Group provided retrospective data from January 2007 to December 2016 for patients with primary RPS who underwent PD along with the total number of consecutive resections done during the same time period. Data from participating centers were combined for analysis.Results
In total, 29 patients underwent PD among 2068 resections performed for primary RPS (1.4%). The predominant histologic subtypes were liposarcoma and leiomyosarcoma. All PD patients underwent concomitant resection of additional organs (median: 2, range: 1–5), including 13 patients (45%) who also received vena cava resection. Definitive evidence of microscopic invasion of the duodenum or pancreas was seen in 84% of patients. Postoperatively, 10 patients (34%) had major complications including 8 (28%) that developed a clinically-significant pancreatic leak. One postoperative death (3.4%) occurred. With a median follow-up of 4.8 years, 19 patients (66%) developed disease recurrence. The patterns of recurrence were dependent on histologic subtype.Conclusion
Although infrequent, when PD is done for primary RPS, resection of additional organs is often required and major complication rates are moderate. The recurrence rate is overall high and the pattern of recurrence is dictated by histologic subtype. 相似文献88.
Studies of motility in Physarum polycephalum have concentrated on the well-defined actomyosin system in plasmodia. It is clear from recent genetic studies in lower eukaryotes that myosin is involved in a number of physiological processes in addition to the contractile functions previously asciibed to the classical type II myosins. Moreover, the myosin protein family has proved to be more complex than anticipated, with an increasing number of reported specialized isoforms. Although a myosin type II activity has been identified in both amoebae and plasmodia of P. polycephalum, and it has been inferred that these proteins undergo a phasespecific isoform switch during development, this phenomenon has not been analysed genetically. In an effort to understand the putative developmental expression of actomyosin-associated proteins, we isolated a 180-kDa protein from amoebae which is highly enriched, along with actin and myosin, in actomyosin preparations in the presence of mM concentrations of Mg++ ions and 10 mM of ATP. Using polyclonal antisera raised against pl80 we have cloned and sequenced a partial cDNA encoding a protein whose predicted amino-acid sequence indicates some similarity with the Dictyostelium discoideum myosin heavy-chain tail domain. Southern-blot and RFLP analyses indicate that the gene involved, designated mlpA (myosin-like protein), occurs in a single copy in the genome, is a novel Physarum gene and is expressed during amoebal and plasmodial growth and in the dormant forms of both these cell types. 相似文献
89.
Roberto Iacovelli Franco Nolè Elena Verri Giuseppe Renne Chiara Paglino Matteo Santoni Maria Cossu Rocca Palma Giglione Gaetano Aurilio Daniela Cullurà Stefano Cascinu Camillo Porta 《Targeted oncology》2016,11(2):143-148
Background
Several clinical trials have reported that therapies targeting programmed death-1 (PD1) and its ligand (PD-L1) improve patient outcomes, while tumor response has been related to PD-L1 expression.Objective
To investigate the prognostic role of PD-L1 expression in patients affected by renal cell carcinoma (RCC).Methods
MEDLINE/PubMed, the Cochrane Library, and ASCO University were searched for studies investigating the prognostic role of PD-L1 expression in RCC. Data extraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.Results
Six studies and 1323 cases were included in the final analysis. PD-L1 was expressed in 24.2 % of clear cell tumors compared to 10.9 % of non-clear cell tumors (p?=?0.002). In the overall population, a higher level of PD-L1 expression increased the risk of death by 81 % (HR; 1.81, 95 % CI 1.31–2.49; p?<?0.001). When the analysis was restricted to cases evaluated by immunohistochemistry alone, the higher expression of PD-L1 more than doubled the risk of death (HR; 2.05, 95 % CI 1.38–3.05; p?<?0.001). In clear cell histology, higher PD-L1 expression increased the risk of death by 53 % (HR; 1.53, 95 % CI 1.27–1.84; p?<?0.001), while in metastatic patients, the evaluation of PD-L1 expression on primary tumors revealed that it retains its prognostic role (HR; 1.45, 95 % CI 1.08–1.93; p?=?0.01).Limitations
Significant heterogeneity has been identified among the included studies. As a consequence, cautious interpretation of the results is recommended.Conclusion
This meta-analysis indicates that a higher level of PD-L1 expression is a negative prognostic factor in RCC. Its validation as an independent prognostic factor compared to other traditionally used clinical parameters in localized or advanced disease is recommended.
90.
Vittoria Colia Salvatore Provenzano Carlo Morosi Paola Collini Salvatore Lorenzo Renne Paolo G. Dagrada Claudia Sangalli Angelo Paolo Dei Tos Andrea Marrari Paolo G. Casali Silvia Stacchiotti 《Clinical sarcoma research》2016,6(1):16