全文获取类型
收费全文 | 455篇 |
免费 | 28篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 5篇 |
儿科学 | 4篇 |
妇产科学 | 8篇 |
基础医学 | 94篇 |
口腔科学 | 11篇 |
临床医学 | 25篇 |
内科学 | 86篇 |
皮肤病学 | 4篇 |
神经病学 | 62篇 |
特种医学 | 6篇 |
外科学 | 19篇 |
综合类 | 30篇 |
预防医学 | 11篇 |
眼科学 | 8篇 |
药学 | 64篇 |
中国医学 | 6篇 |
肿瘤学 | 47篇 |
出版年
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 11篇 |
2020年 | 9篇 |
2019年 | 10篇 |
2018年 | 16篇 |
2017年 | 12篇 |
2016年 | 15篇 |
2015年 | 11篇 |
2014年 | 31篇 |
2013年 | 26篇 |
2012年 | 15篇 |
2011年 | 24篇 |
2010年 | 22篇 |
2009年 | 21篇 |
2008年 | 32篇 |
2007年 | 32篇 |
2006年 | 36篇 |
2005年 | 22篇 |
2004年 | 22篇 |
2003年 | 19篇 |
2002年 | 17篇 |
2001年 | 16篇 |
2000年 | 16篇 |
1999年 | 7篇 |
1998年 | 6篇 |
1997年 | 8篇 |
1996年 | 1篇 |
1995年 | 10篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 2篇 |
1991年 | 1篇 |
1989年 | 1篇 |
1988年 | 1篇 |
排序方式: 共有490条查询结果,搜索用时 15 毫秒
1.
2.
3.
We examined the expression of Na(+)/K(+)-ATPase alpha-subunit isoforms in rat salivary glands by RT-PCR. Isoform alpha1 was expressed strongly in all three major salivary glands. The alpha2 isoform was expressed in both submandibular gland (SMG) and sublingual gland (SLG) but faintly in the parotid gland (PG). The alpha3 was detected only in the SLG, and the alpha3 mRNA in the SLG was 1/8 of its level in the brain. Na(+)/K(+)-ATPase alpha3 isoform in the SLG, was localized predominantly on the basolateral plasma membranes in serous cells by immunohistochemical method. We also found the presence of natural antisense RNA of the alpha3 isoform in rat SLG: the 1st-strand cDNA prepared with gene-specific forward primers targeted to the CDS region and to the promoter region of the alpha3 gene in place of oligo(dT) or gene-specific reverse primers produced reasonable PCR products corresponding to the alpha3 cDNA sequence by the subsequent PCR reaction. Synthesis of the 1st-strand cDNA with the gene-specific forward primers was prevented by RNase digestion of the total RNA preparation, indicating that the PCR products in the RT-PCR system were not due to the contaminated genomic DNA, if any. The alpha3 protein level in rat SLG increased with aging, and levels of both alpha3 mRNA (sense RNA) and alpha3 antisense RNA were higher in SLGs of aged rats than in those of young rats, respectively. 相似文献
4.
Friedlander AH Weinreb J Friedlander I Yagiela JA 《Journal of the American Dental Association (1939)》2007,138(2):179-87; quiz 248
BACKGROUND: The dental literature contains little information about metabolic syndrome (MetS) and its dental implications. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search for the period 2000 through 2005, using the term "metabolic syndrome" to define its pathophysiology, medical treatment and dental implications. RESULTS: MetS is the co-occurrence of abdominal obesity, hyper-triglyceridemia, reduced high-density lipoprotein cholesterol levels, hypertension and impaired fasting glucose, which results from consumption of a high-calorie diet and decreased levels of physical activity superimposed on the appropriate genetic setting. Components of MetS synergistically promote the development of atherosclerosis, resulting in myocardial infarction and stroke. CLINICAL IMPLICATIONS: Deteriorating oral health status is associated with worsening of the atherogenic profile. Tooth loss often results in chewing difficulties because of inadequate occlusive surfaces and may lead to alterations in food selection and dietary quality. This, in turn, adversely affects body composition and nutritional status, both of which are related to vascular health. Dentists should develop treatment plans that preserve and restore the dentition, thus ensuring maximum masticatory efficiency and affording patients the optimum opportunity to consume food that will not foster atherogenesis. 相似文献
5.
《Neuromuscular disorders : NMD》2014,24(3):227-240
The prevailing pathomechanistic paradigm for myotonic dystrophy (DM) is that aberrant expression of embryonic/fetal mRNA/protein isoforms accounts for most aspects of the pleiotropic phenotype. To identify aberrant isoforms in skeletal muscle of DM1 and DM2 patients, we performed exon-array profiling and RT-PCR validation on the largest DM sample set to date, including Duchenne, Becker and tibial muscular dystrophy (NMD) patients as disease controls, and non-disease controls. Strikingly, most expression and splicing changes in DM patients were shared with NMD controls. Comparison between DM and NMD identified almost no significant differences. We conclude that DM1 and DM2 are essentially identical for dysregulation of gene expression, and DM expression changes represent a subset of broader spectrum dystrophic changes. We found no evidence for qualitative splicing differences between DM1 and DM2. While some DM-specific splicing differences exist, most of the DM splicing differences were also seen in NMD controls. SSBP3 exon 6 missplicing was observed in all diseased muscle and led to reduced protein. We conclude there is no widespread DM-specific spliceopathy in skeletal muscle and suggest that missplicing in DM (and NMD) may not be the driving mechanism for the muscle pathology, since the same pathways show expression changes unrelated to splicing. 相似文献
6.
HDAC6 inhibition results in tau acetylation and modulates tau phosphorylation and degradation in oligodendrocytes 下载免费PDF全文
Histone deacetylase 6 (HDAC6) is a unique member of the HDAC family. It is localized within the cytoplasm and has unique substrate specificities for nonhistone proteins, such as α‐tubulin. Furthermore, it plays a major role in protein aggregate formation and recently was demonstrated to interact with the microtubule associated protein tau and tau was identified as a possible substrate for HDAC6 in neurons. This study was undertaken to investigate whether HDAC6 is present in oligodendrocytes and whether it is involved in tubulin and tau acetylation in these cells. We show for the first time that HDAC6 is expressed in cultured rat brain oligodendrocytes. Its inhibition by the specific HDAC6 inhibitor tubastatin A (TST) leads to morphological alterations, microtubule bundling, and tubulin acetylation, and changes in tau‐isoform expression and phosphorylation. Furthermore, the microtubule binding activity of tau was reduced. Using the oligodendroglial cell lines OLN‐t40 and OLN‐t44, which were genetically engineered to express either the longest human tau isoform with four microtubule binding repeats (4R‐tau), or the shortest tau isoform with three repeats (3R‐tau), respectively, we demonstrate that tau is acetylated by HDAC6 within the 4R‐binding domain. Tau acetylation reduced its turnover rate and acetylated tau was degraded slower in these cells. TST and shRNA‐mediated knockdown of HDAC6 in oligodendroglia cells caused an increase in pathological hyperphosphorylated tau detectable with the 12E8 antibody. Hence HDAC6 and dysregulation of the deacetylation and acetylation process in oligodendrocytes may contribute to diseases with oligodendroglial pathology. GLIA 2014;62:535–547 相似文献
7.
8.
A range of studies have shown that the complex process of implantation and an establishment of a pregnancy also involves immune factors. Disturbances in these underlying immune mechanisms might lead to implantation and pregnancy failure and may be involved in the pathogenesis of unexplained infertility. Several studies have reported that imbalances in uterine NK (uNK) cell abundance are associated with infertility; however, controversies exist. An increased amount of CD56+ uNK cells along with a decrease in CD16+ uNK cells have been associated with normal fertility in some studies. Very few studies of FoxP3+ regulatory T cells (Tregs) in the pre-implantation endometrium have been performed. Results are sparse and controversial, studies reporting both increased and decreased numbers of Tregs, respectively, in women suffering from infertility. In conclusion, studies imply that uNK cells, Tregs and HLA-G carry pivotal roles regarding the establishment of a healthy pregnancy, and that abnormal immune mechanisms involving these parameters may be associated with infertility. However, more research in early phases of the reproductive cycle, such as investigating the conditions in the endometrium before implantation, is needed to further clarify the underlying mechanisms. 相似文献
9.
Haochang Hu Cong Zhou Bin Li Yanfei Chen Jie Dai Yiyi Mao Tianyi Huang Hang Yu Min Chen Jun Zhao Shiwei Duan 《Pathology, research and practice》2018,214(10):1572-1578
Purpose
Ras association domain family 1 isoform A (RASSF1A), a member of Ras association domain family, plays an important role in tumorigenesis. The goal of our meta-analysis was to assess the diagnostic value of RASSF1A hypermethylation in colorectal cancer (CRC).Methods
PubMed, Embase, CNKI and Wanfang databases were used to conduct literature selection. The association between RASSF1A methylation and CRC risk was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Summary receiver operating characteristics (SROC) test was used to estimate the diagnostic value of RASSF1A methylation for CRC.Results
A total of 22 articles among 1736 CRC and 811 non-tumor samples were included in the current meta-analysis. Our results showed that RASSF1A hypermethylation was found more frequently in CRC than non-tumor samples (OR?=?6.02, 95% CI?=?4.57–7.93, P?<? 0.001). Our SROC test showed that RASSF1A hypermethylation had an area under the curve (AUC) of 0.71 with a pooled sensitivity of 0.33 (95% CI?=?0.31–0.36), a pooled specificity of 0.86 (95% CI?=?0.84–0.89), a positive-likelihood ratio of 3.18 (95% CI?=?1.99–5.09), a negative-likelihood ratio of 0.71 (95% CI?=?0.63–0.80), and a diagnostic odds ratio of 5.53 (95% CI?=?3.40–9.00). Data mining study indicated that a trend of increased RASSF1A expression was found in the CRC cell line C2C12 after 5-AZA treatment.Conclusions
Our study established that RASSF1A hypermethylation might have a potential value in the clinical diagnosis of CRC. 相似文献10.
目的 探讨组织蛋白酶D(CTSD)新的糖基化异构体与肺癌临床病理特征及预后的相关性。 方法 应用免疫组织化学和半定量RT PCR方法检测119例肺癌组织和39例癌旁组织中CTSD的表达;Western blotting分析CTSD各异构体表达特点;去糖基化实验检测CTSD 蛋白的糖基化修饰;Kaplan-Meier分析66kD异构体、临床病理资料与肺癌术后整体生存期的相关性。 结果 CTSD在肺鳞癌、腺癌和小细胞肺癌组织中高表达;66kD蛋白为CTSD新的糖基化异构体,该异构体表达与肺癌组织类型、临床分期、淋巴结转移和患者的吸烟史密切相关(P<0.05),阳性表达和阴性表达患者术后中位生存时间分别为20.0和30.0个月(P<0.05);肺癌组织类型、临床分期、淋巴结转移、肿瘤大小和66kD异构体表达是影响肺癌预后的独立因素。 结论 CTSD 66kD异构体阳性表达可能是肺癌预后不良的分子标志物之一。 相似文献