全文获取类型
收费全文 | 1746篇 |
免费 | 115篇 |
国内免费 | 7篇 |
专业分类
耳鼻咽喉 | 18篇 |
儿科学 | 81篇 |
妇产科学 | 125篇 |
基础医学 | 234篇 |
口腔科学 | 121篇 |
临床医学 | 125篇 |
内科学 | 298篇 |
皮肤病学 | 40篇 |
神经病学 | 132篇 |
特种医学 | 35篇 |
外科学 | 380篇 |
综合类 | 7篇 |
一般理论 | 3篇 |
预防医学 | 47篇 |
眼科学 | 11篇 |
药学 | 61篇 |
中国医学 | 1篇 |
肿瘤学 | 149篇 |
出版年
2023年 | 16篇 |
2022年 | 29篇 |
2021年 | 35篇 |
2020年 | 21篇 |
2019年 | 32篇 |
2018年 | 46篇 |
2017年 | 27篇 |
2016年 | 43篇 |
2015年 | 38篇 |
2014年 | 70篇 |
2013年 | 70篇 |
2012年 | 103篇 |
2011年 | 132篇 |
2010年 | 57篇 |
2009年 | 62篇 |
2008年 | 117篇 |
2007年 | 128篇 |
2006年 | 96篇 |
2005年 | 95篇 |
2004年 | 106篇 |
2003年 | 95篇 |
2002年 | 92篇 |
2001年 | 26篇 |
2000年 | 20篇 |
1999年 | 27篇 |
1998年 | 17篇 |
1997年 | 19篇 |
1996年 | 19篇 |
1995年 | 13篇 |
1994年 | 9篇 |
1993年 | 7篇 |
1992年 | 17篇 |
1991年 | 19篇 |
1990年 | 19篇 |
1989年 | 20篇 |
1988年 | 15篇 |
1987年 | 18篇 |
1986年 | 11篇 |
1985年 | 8篇 |
1983年 | 7篇 |
1981年 | 4篇 |
1979年 | 8篇 |
1978年 | 9篇 |
1977年 | 3篇 |
1976年 | 7篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 4篇 |
1967年 | 3篇 |
排序方式: 共有1868条查询结果,搜索用时 15 毫秒
21.
D Eidelman 《Medical hypotheses》1979,5(3):339-346
"Fatigue on Rest", headache, vertigo and the feeling of loss of balance, blurred vision, nausea, tension and irritability, were found to be prevalent amongst patients who had locally asymptomatic, unerupted impacted teeth. A comparative pressure sign was developed, which, when positive, confirmed the relationship between the impacted teeth and the medical symptoms. Removal of the impactions resulted in the alleviation of the symptoms. Stress and psychogenic factors are considered as trigger mechanisms, rather than as basic causes of the symptoms. 相似文献
22.
Jesús Ruiz-Cabello Kirsten Berghmans Ofer Kaplan Marc E. Lippman Robert Clarke Jack S. Cohen 《Breast cancer research and treatment》1995,33(3):209-217
Many breast tumors appear to progress from estrogen-dependent growth to a more malignant phenotype characterized by estrogen-independent growth, antiestrogen resistance, and a high metastatic potential. Utilizing31P NMR spectroscopy on human breast cancer cells growingin vitro, we have investigated the effects of 17-estradiol and tamoxifen on the metabolic/bioenergetic spectra of a series of human breast cancer cells that vary in their estrogen and antiestrogen responsiveness. A comparison of baseline spectra associates higher levels of phosphodiesters and UDP-glucosides (e.g. UDP-glucose, UDP-N-acetylglucosamine), and lower phosphocholine/glycerylphosphocholine and phosphocholine/phosphoethanolamine ratios, with the acquisition of estrogen-independent growth in estrogen receptor expressing cells. No metabolic changes are clearly associated with the metastatic phenotype. Whilst estrogen treatment produces no consistently significant spectral changes in any of the cell lines, the estrogen-independent and estrogen-responsive MCF7/MIII cell line responds to tamoxifen treatment by significantly increasing all spectral resonances 30%-40% above baseline values. This may reflect a tamoxifen-induced change to a more differentiated or apoptotic phenotype, or an attempt by the cells to reverse the inhibitory effects of the drug. The ability to detect metabolic changes in response to tamoxifen by NMR spectroscopy may provide a novel means to identify those tumors that are responsive to antiestrogen therapy.Abbreviations CCS-IMEM
steroid-deprived Improved Minimal Essential Medium
- E2
17-estradiol
- ER
estrogen receptor
- Pi
inorganic phosphate
- GPE
glyceryl-phosphoethanolamine
- GPC
glyceryl-phosphocholine
- PC
phosphocholine
- PE
phosphoethanolamine
- PDE
phosphodiesters
- PME
phosphomonoesters
- TAM
tamoxifen (trans-1-(4--dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene)
- UDPG
uridine diphosphoglycoside 相似文献
23.
Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients. 总被引:4,自引:0,他引:4
Meera Srivastava Lukas Bubendorf Mark Raffeld Christoph Bucher Jochen Torhorst Guido Sauter Cara Olsen Olli P Kallioniemi Ofer Eidelman Harvey B Pollard 《Clinical cancer research》2004,10(7):2344-2350
PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients. 相似文献
24.
Antonio Vivi Maria Tassini Hava Ben-Horin Gil Navon Ofer Kaplan 《Breast cancer research and treatment》1997,43(1):15-25
Lonidamine (LND) is a relatively new anti-cancer drug,and several clinical trials have indicated that it may be effectivein combinations with other therapeutic modalities. LND isclassified within the metabolic inhibitor agents. Multidrugresistance (MDR) phenomenon is often associated with increasedenergy requirements, and enhanced glycolysis rate. These studieswere performed to delineate the mechanism of action of LNDon MDR human breast cancer cells, and to investigate whetherLND as a single agent, or in combination with anotheranti-metabolism drug, 2-deoxyglucose (2-DG), may be usefulagainst MDR tumors. The effects of LND on intact perfuseddrug-sensitive (WT) and 33-fold resistant to Adriamycin(Adr) MCF-7 cells, embedded in alginate micro capsules, were continuouslymonitored by 31P and 13C nuclearmagnetic resonance (NMR) spectroscopy. 31PNMR studies showed that LND induced intracellular acidificationand depletion of NTP in both WT and Adr cells. However, pH and NTPlevels decreased less in the Adr cells than in the WT cells(p < 0.05 for both parameters). 13CNMR demonstrated that LND inhibited lactate transport,and lactate signals were elevated in both cell lines. However, theintracellular lactate levels increased to a greater extentin the WT than in the Adr cells (p < 0.05).There were major differences in the effects of LND onmetabolism between sensitive and resistant cells.While LND enhanced glucose uptake in the WT cells, and itsadministration was followed by continuous increase oflactate signal, both processes were not affected by LNDin the Adr cells. 2-DG is a glucose analogue that inhibitsboth cellular uptake and utilization of glucose, leading to cell starvation. Combined treatment with LND and2-DG yielded at best additive, but not synergistic,cellular toxicity, and the metabolic effects of LNDwere attenuated by 2-DG. These results showed that the principalmechanism of action of LND is inhibition of lactate transportleading to intracellular lactate accumulation and acidificationin both WT and Adr cells. The Adr cells were only 2-fold resistantto LND (compared to the WT cells), and since cellular uptakeof alkaloid chemotherapy is improved in acidic environment,LND may have a role in the treatment protocols of MDR tumors,especially when given as the initial means for inductionof intracellular acidification. 相似文献
25.
Baruch Modan Angela Chetrit Esther Alfandary Arnon Tamir Ayala Lusky Michael Wolf Ofer Shpilberg 《The Laryngoscope》1998,108(7):1095-1097
Objective: To assess the risk of neoplastic development among persons exposed to scalp irradiation. Study Design: Historical cohort study initially; prospective follow-up subsequently. Method: Two control groups—population and siblings—matched for age, sex, ethnic origin, and year of immigration. Follow-up from time of irradiation (1950s) until the end of 1991. Linkage with nationwide cancer registry. Results: A 4.5–fold incidence of cancer (P < .01) and a 2.6–fold increase of benign tumors were noted. The mean length of latency period until tumor development was 11 years for malignant tumors and 21.5 years for benign. A clear dose response effect for both cancer and benign tumors was demonstrated. Conclusions: The study confirms the role of radiation in salivary gland carcinogenesis. It indicates a need for better awareness, a comprehensive examination, and long-term follow-up of patients who have been subjected to head and neck radiation. 相似文献
26.
M Kaplan E Kaplan C Hammerman N Algur R Bromiker M S Schimmel A I Eidelman 《Archives of disease in childhood》2006,91(1):31-34
AIM: To determine the incidence of post-phototherapy neonatal plasma total bilirubin (PTB) rebound. METHODS: A prospective clinical survey was performed on 226 term and near-term neonates treated with phototherapy in the well baby nursery of the Shaare Zedek Medical Center from January 2001 to September 2002. Neonates were tested for PTB 24 hours (between 12 and 36 hours) after discontinuation of phototherapy, with additional testing as clinically indicated. The main outcome measure, significant bilirubin rebound, was defined as a post-phototherapy PTB > or =256 micromol/l. Phototherapy was not reinstituted in all cases of rebound, but rather according to clinical indications. RESULTS: A total of 30 (13.3%) neonates developed significant rebound (mean (SD) PTB 287 (27) micromol/l, upper range 351 micromol/l). Twenty two of these (73%) were retreated with phototherapy at mean PTB 296 (29) micromol/l. Multiple logistic regression analysis showed significant risk for aetiological risk factors including positive direct Coombs test (odds ratio 2.44, 95% CI 1.25 to 4.74) and gestational age <37 weeks (odds ratio 3.21, 95% CI 1.29 to 7.96). A greater number of neonates rebounded among those in whom phototherapy was commenced < or =72 hours (26/152, 17%) compared with >72 hours (4/74, 5.4%) (odds ratio 3.61, 95% CI 1.21 to 10.77). CONCLUSION: Post-phototherapy neonatal bilirubin rebound to clinically significant levels may occur, especially in cases of prematurity, direct Coombs test positivity, and those treated < or =72 hours. These risk factors should be taken into account when planning post-phototherapy follow up. 相似文献
27.
Although symptoms of acute stress disorder or PTSD in the aftermath of physical trauma may be a reason for psychiatric referral, little has been written on the management of patients in this context. We report the possible benefit of risperidone, an atypical antipsychotic, in 4 cases where flashbacks were reported in patients hospitalized for the treatment of physical trauma. 相似文献
28.
29.
Nicole A. Najor Lauren Albrecht Natalia Malchin Tomer Goldsmith Meital Grafi‐Cohen Dan Vodo Gilad Fainberg Benjamin Meilik Ilan Goldberg Emily Warshauer Tova Rogers Sarah Edie Akemi Ishida‐Yamamoto Lisa Burzenski Noam Erez Steve A. Murray Alan D. Irvine Lenny Shultz Kathleen J. Green Jouni Uitto Eli Sprecher Ofer Sarig 《Experimental dermatology》2017,26(5):423-430
SVEP1 is a recently identified multidomain cell adhesion protein, homologous to the mouse polydom protein, which has been shown to mediate cell‐cell adhesion in an integrin‐dependent manner in osteogenic cells. In this study, we characterized SVEP1 function in the epidermis. SVEP1 was found by qRT‐PCR to be ubiquitously expressed in human tissues, including the skin. Confocal microscopy revealed that SVEP1 is normally mostly expressed in the cytoplasm of basal and suprabasal epidermal cells. Downregulation of SVEP1 expression in primary keratinocytes resulted in decreased expression of major epidermal differentiation markers. Similarly, SVEP1 downregulation was associated with disturbed differentiation and marked epidermal acanthosis in three‐dimensional skin equivalents. In contrast, the dispase assay failed to demonstrate significant differences in adhesion between keratinocytes expressing normal vs low levels of SVEP1. Homozygous Svep1 knockout mice were embryonic lethal. Thus, to assess the importance of SVEP1 for normal skin homoeostasis in vivo, we downregulated SVEP1 in zebrafish embryos with a Svep1‐specific splice morpholino. Scanning electron microscopy revealed a rugged epidermis with perturbed microridge formation in the centre of the keratinocytes of morphant larvae. Transmission electron microscopy analysis demonstrated abnormal epidermal cell‐cell adhesion with disadhesion between cells in Svep1‐deficient morphant larvae compared to controls. In summary, our results indicate that SVEP1 plays a critical role during epidermal differentiation. 相似文献
30.
The use of the hydrodynamic HBV animal model to study HBV biology and anti-viral therapy. 总被引:1,自引:0,他引:1
Mali Ketzinel-Gilad Arie Zauberman Ofer Nussbaum Yariv Shoshany Ofer Ben-Moshe Orit Pappo Yaakov Felig Ehud Ilan Hanna Wald Shlomo Dagan Eithan Galun 《Hepatology research》2006,34(4):228-237
A simple reproducible and versatile small animal model for hepatitis B virus (HBV) infection is still unavailable. We have generated a simple transient liver-targeted transgenic mouse. Hydrodynamics tail vein injection of a head-to-tail dimer of adw HBV genome (pHBVadwHTD) into immunocompetent mice generated HBsAg and HBeAg expression in both serum and hepatocytes, followed by seroconversion. The injection of pHBVadwHTD into SCID mice generated prolonged HBsAg and HBeAg antigenemia and HBV viremia. Our results demonstrate that hydrodynamic injection of naked DNA could support the generation of HBV particles. We used this model for the assessment of anti-viral agents. Administration of our human monoclonal antibodies, HBV-Ab17(XTL) and HBV-Ab19(XTL), as well as Lamivudine (3TC) treatment suppressed HBV viremia. The model presented herein supports long and stable expression of HBV and will enable determination of various biological questions related to HBV life cycle, mutants and could enhance the development of anti-viral reagents. 相似文献