全文获取类型
收费全文 | 347篇 |
免费 | 44篇 |
国内免费 | 1篇 |
专业分类
耳鼻咽喉 | 2篇 |
儿科学 | 17篇 |
妇产科学 | 14篇 |
基础医学 | 47篇 |
口腔科学 | 2篇 |
临床医学 | 33篇 |
内科学 | 64篇 |
皮肤病学 | 10篇 |
神经病学 | 43篇 |
特种医学 | 26篇 |
外科学 | 50篇 |
综合类 | 13篇 |
预防医学 | 27篇 |
眼科学 | 5篇 |
药学 | 11篇 |
肿瘤学 | 28篇 |
出版年
2023年 | 5篇 |
2022年 | 10篇 |
2021年 | 14篇 |
2020年 | 13篇 |
2019年 | 10篇 |
2018年 | 11篇 |
2017年 | 5篇 |
2016年 | 10篇 |
2015年 | 11篇 |
2014年 | 18篇 |
2013年 | 25篇 |
2012年 | 25篇 |
2011年 | 33篇 |
2010年 | 8篇 |
2009年 | 11篇 |
2008年 | 12篇 |
2007年 | 7篇 |
2006年 | 13篇 |
2005年 | 17篇 |
2004年 | 5篇 |
2003年 | 9篇 |
2002年 | 8篇 |
2001年 | 7篇 |
2000年 | 6篇 |
1999年 | 3篇 |
1997年 | 2篇 |
1996年 | 2篇 |
1995年 | 3篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 8篇 |
1990年 | 7篇 |
1989年 | 4篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 3篇 |
1985年 | 4篇 |
1984年 | 3篇 |
1979年 | 4篇 |
1977年 | 2篇 |
1976年 | 2篇 |
1974年 | 2篇 |
1973年 | 2篇 |
1970年 | 2篇 |
1969年 | 3篇 |
1967年 | 6篇 |
1966年 | 3篇 |
1965年 | 2篇 |
1962年 | 2篇 |
1958年 | 2篇 |
排序方式: 共有392条查询结果,搜索用时 11 毫秒
1.
An inhibitor of the production of interferon ("blocker") 总被引:4,自引:0,他引:4
2.
Polysomnographic and actigraphic evidence of sleep fragmentation in patients with irritable bowel syndrome 总被引:3,自引:0,他引:3
STUDY OBJECTIVE: To characterize the function and quality of sleep in patients with irritable bowel syndrome (IBS). DESIGN: A prospective study with a historic comparison group. SETTING: A regional hospital that also serves as a tertiary referral center. PATIENTS: Eighteen patients with IBS and a comparison group of 20 matched adults with mild benign snoring. INTERVENTIONS: A polysomnography study and a wrist actigraphy study. MEASUREMENTS: All subjects underwent sleep studies and completed self-report questionnaires (IBS severity, psychosocial variables, sleep function, and Epworth Sleepiness Scale). Fourteen IBS and 11 comparison patients underwent actigraphy. RESULTS: The IBS patients had more than 70% less slow-wave stage sleep (4.5 +/- 7.3% vs 19.3 +/- 12.9%; P = 0.006), compensated by increased stage 2 sleep (72.2 +/- 6.6% vs 60.1 +/- 16.8%; P = 0.01). The IBS group had significant sleep fragmentation with a significantly higher arousal and awakening index (P < 0.001), a longer wake period after sleep onset (P = 0.02), and more downward shifts to lighter sleep stages (P = 0.01). The 4-night actigraphy study supported the polysomnography findings. The sleep fragmentation index was significantly higher (P = 0.008) in the IBS group. The IBS patients reported greater daytime sleepiness (9.0 +/- 4.8 vs 6.4 +/- 4.8, Epworth Sleepiness Scale score, P < 0.01) and greater impairment in quality of life, which correlated significantly with the sleep fragmentation indexes. The difference between the groups was not due to differences in baseline anxiety/depression levels. CONCLUSIONS: Patients with IBS have impaired sleep quality, reduced slow-wave sleep activity, and significant sleep fragmentation. The cause-and-effect relationship of these findings with patients' daytime symptoms should be studied further. 相似文献
3.
I Kremer J Sandbank D Weinberger A Rotem A Shapiro 《The British journal of ophthalmology》1992,76(5):294-296
Two out of 60 conjunctival epithelial tumours reviewed between 1973 and 1989 were found to be pigmented. One tumour was a pigmented papilloma and the other a pigmented squamous cell carcinoma. The melanin pigment was found in epithelial tumour cells as well as in macrophages, dendritic melanocytes, and Langerhans cells. The distinction between the latter two types of cells was possible in one of the tumours only. Both tumours were found in dark-skinned white patients without any evidence of conjunctival acquired melanosis. 相似文献
4.
Bar-Oz B Diav-Citrin O Shechtman S Tellem R Arnon J Francetic I Berkovitch M Ornoy A 《European journal of obstetrics, gynecology, and reproductive biology》2008,141(1):31-34
Objectives
To determine whether the use of the new macrolides (azithromycin, clarithromycin, roxithromycin) during the first trimester of pregnancy is associated with an increased risk of major malformations.Study design
In a prospective multi-center study, pregnancy outcome was compared between pregnant women exposed to one of the new macrolides during the first trimester of pregnancy and two comparison groups one exposed to other antibiotics and the other to other non-teratogenic medications. All women enrolled in the study called one of the three participating teratogen information services (TIS). Group 1 macrolides (n = 161), group 2 other antibiotics (n = 213) and group 3 non-teratogens (n = 740).Results
A total of 161 women exposed to the new macrolides (118 were exposed in the first trimester of pregnancy) and 953 from a comparison groups were followed up. The rate of major malformations in the study group was 4.1% compared to 2.1% in the other antibiotics exposed group (OR = 1.41, 95% CI 0.47–4.23) and 3.0% in the non-teratogens exposed group. The rate of elective terminations of pregnancy was significantly higher in the exposed group in compare to both comparison groups.Conclusion
Our study, although relatively small sized, suggests that the use of the new macrolides during the first trimester of pregnancy does not represent an increased risk for congenital malformations strong enough for an induced abortion after such an exposure. Elective terminations of pregnancy because of early exposure to these medications should be reconsidered. 相似文献5.
Rivki Cashman Helit Cohen Rotem Ben-Hamo Alona Zilberberg Sol Efroni 《Oncotarget》2014,5(4):1071-1082
Identifying novel mechanisms, which are at the core of breast cancer biology, is of critical importance. Such mechanisms may explain response to treatment, reveal novel targets or drive detection assays.To uncover such novel mechanisms, we used survival analysis on gene expression datasets encompassing 1363 patients. By iterating over the compendia of genes, we screened for their significance as prognosis biomarkers and identified SUMO-specific protease 5 (SENP5) to significantly stratify patients into two survival groups across five unrelated tested datasets. According to these findings, low expression of SENP5 is associated with good prognosis among breast cancer patients.Following these findings, we analyzed SENP5 silencing and show it is followed by inhibition of anchorage-independence growth, proliferation, migration and invasion in breast cancer cell lines. We further show that these changes are conducted via regulation of TGFβRI levels. These data relate to recent reports about the SUMOylation of TGFβRI. Following TGFβRI changes in expression, we show that one of its target genes, MMP9, which plays a key role in degrading the extracellular matrix and contributes to TGFβ-induced invasion, is dramatically down regulated upon SENP5 silencing.This is the first report represents SENP5-TGFβ-MMP9 cascade and its mechanistic involvement in breast cancer. 相似文献
6.
Karni R Hippo Y Lowe SW Krainer AR 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(40):15323-15327
The splicing factor SF2/ASF is an oncoprotein that is up-regulated in many cancers and can transform immortal rodent fibroblasts when slightly overexpressed. The mTOR signaling pathway is activated in many cancers, and pharmacological blockers of this pathway are in clinical trials as anticancer drugs. We examined the activity of the mTOR pathway in cells transformed by SF2/ASF and found that this splicing factor activates the mTORC1 branch of the pathway, as measured by S6K and eIF4EBP1 phosphorylation. This activation is specific to mTORC1 because no activation of Akt, an mTORC2 substrate, was detected. mTORC1 activation by SF2/ASF bypasses upstream PI3K/Akt signaling and is essential for SF2/ASF-mediated transformation, as inhibition of mTOR by rapamycin blocked transformation by SF2/ASF in vitro and in vivo. Moreover, shRNA-mediated knockdown of mTOR, or of the specific mTORC1 and mTORC2 components Raptor and Rictor, abolished the tumorigenic potential of cells overexpressing SF2/ASF. These results suggest that clinical tumors with SF2/ASF up-regulation could be especially sensitive to mTOR inhibitors. 相似文献
7.
Shulamit Sebban Regina Golan-Gerstl Rotem Karni Olga Vaksman Ben Davidson Reuven Reich 《Clinical & experimental metastasis》2013,30(1):103-117
We previously found LOXL4 to be alternatively spliced in an anatomic site-specific manner in tumors involving the serosal cavities. LOXL4 splice variants were predominantly or exclusively expressed in effusion specimens from ovarian and breast carcinoma patients, and were absent in primary carcinomas. In the present study, LOXL4 full-length or splice variants were overexpressed in ES-2 and MDA-MB-231 cells and their invasive and metastatic potential and microRNA expression profile were evaluated. ES-2 cells were further injected into SCID mice ovaries and the extent of tumor progression and metastases formation were compared. We show that both splice variants have a positive effect on the metastatic potential of cells in vitro and on tumor progression in vivo. In contrast, full-length LOXL4 is not pro-metastatic, and may even be considered as a tumor suppressor. In addition, we show that LOXL4 is a possible splicing target of the oncogenic splicing factors SRSF1 and hnRNP A1. In conclusion, our results point to a significant role for LOXL4 alternative splicing in tumor progression. 相似文献
8.
Michal Cohen‐Eliav Regina Golan‐Gerstl Zahava Siegfried Claus L Andersen Kasper Thorsen Torben F Ørntoft David Mu Rotem Karni 《The Journal of pathology》2013,229(4):630-639
An increasing body of evidence connects alterations in the process of alternative splicing with cancer development and progression. However, a direct role of splicing factors as drivers of cancer development is mostly unknown. We analysed the gene copy number of several splicing factors in colon and lung tumours, and found that the gene encoding for the splicing factor SRSF6 is amplified and over‐expressed in these cancers. Moreover, over‐expression of SRSF6 in immortal lung epithelial cells enhanced proliferation, protected them from chemotherapy‐induced cell death and converted them to be tumourigenic in mice. In contrast, knock‐down of SRSF6 in lung and colon cancer cell lines inhibited their tumourigenic abilities. SRSF6 up‐ or down‐regulation altered the splicing of several tumour suppressors and oncogenes to generate the oncogenic isoforms and reduce the tumour‐suppressive isoforms. Our data suggest that the splicing factor SRSF6 is an oncoprotein that regulates the proliferation and survival of lung and colon cancer cells. 相似文献
9.
Chen Vincent Barker Alex J. Golan Rotem Scott Michael B. Huh Hyungkyu Wei Qiao Sojoudi Alireza Markl Michael 《The international journal of cardiovascular imaging》2021,37(12):3539-3547
The International Journal of Cardiovascular Imaging - Deep learning algorithms for left ventricle (LV) segmentation are prone to bias towards the training dataset. This study assesses sex- and... 相似文献
10.
Yonatan Perez Libe Gradstein Hagit Flusser Barak Markus Idan Cohen Yshaia Langer Mira Marcus Tova Lifshitz Rotem Kadir Ohad S Birk 《European journal of human genetics : EJHG》2014,22(5):703-706
Foveal hypoplasia, always accompanied by nystagmus, is found as part of the clinical spectrum of various eye disorders such as aniridia, albinism and achromatopsia. However, the molecular basis of isolated autosomal recessive foveal hypoplasia is yet unknown. Individuals of apparently unrelated non consanguineous Israeli families of Jewish Indian (Mumbai) ancestry presented with isolated foveal hypoplasia associated with congenital nystagmus and reduced visual acuity. Genome-wide homozygosity mapping followed by fine mapping defined a 830 Kb disease-associated locus (LOD score 3.5). Whole-exome sequencing identified a single missense mutation in the homozygosity region: c.95T>G, p.(Ile32Ser), in a conserved amino acid within the first predicted transmembrane domain of SLC38A8. The mutation fully segregated with the disease-associated phenotype, demonstrating an ∼10% carrier rate in Mumbai Jews. SLC38A8 encodes a putative sodium-dependent amino-acid/proton antiporter, which we showed to be expressed solely in the eye. Thus, a homozygous SLC38A8 mutation likely underlies isolated foveal hypoplasia. 相似文献