全文获取类型
收费全文 | 3005篇 |
免费 | 215篇 |
国内免费 | 17篇 |
学科分类
医药卫生 | 3237篇 |
出版年
2023年 | 27篇 |
2022年 | 47篇 |
2021年 | 62篇 |
2020年 | 36篇 |
2019年 | 65篇 |
2018年 | 60篇 |
2017年 | 39篇 |
2016年 | 48篇 |
2015年 | 70篇 |
2014年 | 75篇 |
2013年 | 102篇 |
2012年 | 154篇 |
2011年 | 182篇 |
2010年 | 99篇 |
2009年 | 97篇 |
2008年 | 128篇 |
2007年 | 157篇 |
2006年 | 138篇 |
2005年 | 146篇 |
2004年 | 117篇 |
2003年 | 123篇 |
2002年 | 112篇 |
2001年 | 69篇 |
2000年 | 83篇 |
1999年 | 68篇 |
1998年 | 43篇 |
1997年 | 34篇 |
1996年 | 32篇 |
1995年 | 21篇 |
1994年 | 14篇 |
1993年 | 24篇 |
1992年 | 64篇 |
1991年 | 58篇 |
1990年 | 59篇 |
1989年 | 43篇 |
1988年 | 48篇 |
1987年 | 48篇 |
1986年 | 51篇 |
1985年 | 45篇 |
1984年 | 26篇 |
1983年 | 26篇 |
1982年 | 20篇 |
1981年 | 18篇 |
1979年 | 28篇 |
1978年 | 18篇 |
1974年 | 14篇 |
1973年 | 17篇 |
1972年 | 21篇 |
1971年 | 14篇 |
1970年 | 17篇 |
排序方式: 共有3237条查询结果,搜索用时 0 毫秒
61.
Tarek K. Motawi Samy A. Abdelazim Hebatallah A. Darwish Samia A. Shouman 《Nutrition and cancer》2016,68(3):435-445
Despite tamoxifen (TAM) is beneficial in treating a significant proportion of patients with breast cancer, many women still relapse after long-term therapy. Caffeic acid phenethyl ester (CAPE) is a component of honeybee propolis, with a plethora of important biological actions including anticancer activity. This study aimed to explore the cytotoxicity, the type of drugs interaction as well as the apoptotic and autophagic pathways of the combined treatment of TAM and CAPE in MCF-7 cells. Their antitumor activity and effect on survival of mice bearing Ehrlich tumor were also analyzed. The results showed synergistic cytotoxic effects, manifested by significant activation of apoptotic machinery, along with downregulation of protein levels of Bcl-2 and beclin-1, upon using the combination regimen. However, the ratio between microtubule-associated protein light chain 3-II and -I was not altered. Moreover, a decrease in vascular endothelial growth factor level was detected. Similarly, TAM + CAPE increased the life span of tumor-bearing animals and caused a marked regression in their tumor size and weight compared with those treated with either TAM or CAPE alone. In conclusion, CAPE relatively improved the anticancer activity of TAM in both in vitro and in vivo models via its apoptotic and angiostatic potentials. 相似文献
62.
Dalia I. Hamdan Samia S. Hafez Wafaa H. B. Hassan Mai M. Morsi Heba M. A. Khalil Yasmine H. Ahmed Omar A. Ahmed-Farid Riham A. El-Shiekh 《RSC advances》2022,12(6):3476
This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane (DCM) fractions of Morus macroura leaves (L) and stem branches (S) on post-myocardial infarction (MI) depression induced by isoprenaline (ISO) in rats in relation to their metabolites. The study was propped with a UPLC-ESI-MS/MS profiling and chromatographic isolation of the secondary metabolites. Column chromatography revealed the isolation of lupeol palmitate (6) that was isolated for the first time from nature with eight known compounds. In addition, more than forty metabolites belonging, mainly to flavonoids, and anthocyanins groups were identified. The rats were injected with ISO (85 mg kg−1, s.c) in the first two days, followed by the administration of M. macroura DCM-L and DCM-S fractions (200 mg kg−1 p.o) for 19 days. Compared with the ISO exposed rats, the treated rats displayed a reduction in cardiac biomarkers (LDH and CKMB), anxiety, and depressive-like behaviour associated with an increase in the brain defense system (SOD and GSH), neuronal cell energy, GABA, serotonin, and dopamine, confirmed by histopathological investigations. In conclusion, DCM-L and DCM-S fractions'' cardioprotective and anti-depressive activities are attributed to their metabolite profile. Therefore, they could serve as a potential agent in amending post-MI depression.This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane fractions of Morus macroura leaves and stem branches on post-myocardial infarction depression induced by isoprenaline in rats in relation to their metabolites. 相似文献
63.
Ayman El-Garf Samia Salah Iman Iskander Hala Salah Sherif Naseh Amin 《Rheumatology international》2010,30(10):1293-1298
The objective of the study is to screen 12 MEFV gene mutations in Egyptian patients with familial Mediterranean fever (FMF)
and to study the initial hypothesis that the phenotypic expression of the disease may be attributable to the existence of
a particular mutation. We enrolled 136 Egyptian patients (74 males, and 62 females) with a clinical diagnosis of FMF. DNA
was amplified by PCR and subjected to reverse hybridization for the detection of 12 MEFV gene mutations. The phenotypic expression
of the disease was compared in two subgroups according to the presence of homozygote E148Q and M694V gene mutations. The most
frequent gene mutations in the studied group were V726A, M694V, M680I, E148Q and M694I in 41.2, 32.4, 29.4, 25 and 20.6%,
respectively. At least one of these main five founder mutations was present in 132 patients (97.1%). Thirty-two patients (23.5%)
were homozygote for one of the main five founder mutations. The most common homozygote gene mutations were E148Q and M694V,
each in 12 patients (8.8%). Significant increase in abdominal pain and arthritis was found in patients with homozygote M694V
mutation compared to those with E148Q mutation. All patients with amyloidosis had M694V gene mutation. The increased frequency
of V726A gene mutation and the rarity of amyloidosis in this study suggest that Egyptian patients may have a milder form of
FMF compared to other populations. The five main founder mutations account for the vast majority of cases of FMF. M694V gene
mutation may be associated with increased frequency of abdominal pain, arthritis and the presence of amyloidosis. 相似文献
64.
Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: role in epithelio-stromal interactions and matrix metalloproteinase induction 总被引:12,自引:0,他引:12 下载免费PDF全文
Gabison EE Mourah S Steinfels E Yan L Hoang-Xuan T Watsky MA De Wever B Calvo F Mauviel A Menashi S 《The American journal of pathology》2005,166(1):209-219
Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confocal microscopy, zymography, immunoblots, and real-time polymerase chain reaction. In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelio-stromal boundary. The role of epithelial-stromal interaction in MMP induction was investigated in an in vitro co-culture system and demonstrated an induction and co-localization of EMMPRIN and MMP-2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN-containing purified epithelial cell membranes also induced MMP-1, MMP-2, and EMMPRIN and this was inhibited by a blocking anti-EMMPRIN antibody, suggesting that EMMPRIN was primarily responsible for this induction. These findings, and the up-regulation of EMMPRIN by epidermal growth factor and transforming growth factor-beta, demonstrate a role for EMMPRIN in wound healing and suggest that sustained local up-regulation of EMMPRIN and MMPs in chronic situations in which healing is delayed may lead to excessive matrix degradation and corneal melts. 相似文献
65.
Phenotypic stability of the cell wall of Streptococcus mutans Ingbritt grown under various conditions. 下载免费PDF全文
K W Knox N A Jacques L K Campbell A J Wicken S F Hurst A S Bleiweis 《Infection and immunity》1979,26(3):1071-1078
Quantitative analyses of cell walls from Streptococcus mutans Ingbritt grown under carbohydrate limitation in the chemostat showed that growth conditions had no statistically significant effect on the composition of polysaccharide, peptidoglycan, or the proportion of polysaccharide in the cell wall. Lysis of cell wall preparations with a muramidase supported this conclusion and further indicated that there was little difference in their overall structure. In contrast, there was a consistent difference between the rates of lysis by this enzyme of organisms grown in 0.2% glucose and 0.5% glucose. Extremes of pH or dilution rate essentially did not influence the immunogenicity of type c antigen in whole organisms irrespective of whether the carbohydrate source was glucose or sucrose. However, differences were found in the immunogenicity of lipoteichoic acid under similar circumstances. The results indicated there was an inherent phenotypic stability in the cell walls of S. mutans Ingbritt despite changes in pH, generation time, and carbohydrate source, and that any changes that did occur were probably due to associated cell-surface components. 相似文献
66.
RuthMabel Boytz Mikołaj Słabicki Sita Ramaswamy J. J. Patten Charles Zou Chengcheng Meng Brett L. Hurst Jinhua Wang Radosław P. Nowak Priscilla L. Yang Martin Sattler Richard M. Stone James D. Griffin Nathanael S. Gray Suryaram Gummuluru Robert A. Davey Ellen Weisberg 《Journal of medical virology》2023,95(1):e28157
Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response. 相似文献
67.
Zachary C. Lum David A. Crawford Adolph V. Lombardi Jason M. Hurst Michael J. Morris Joanne B. Adams Keith R. Berend 《The Knee》2018,25(1):161-166
Background
Medial unicompartmental knee arthroplasty (UKA) may have advantages over total knee arthroplasty (TKA) in the setting of obesity. There has been no direct comparison between the two cohorts. This study compares outcomes and complications of severely obese patients undergoing medial UKA versus TKA.Methods
Six hundred and fifty medial UKA and 1300 TKA were performed in patients with BMI > 35 kg/m2 (mean 41 kg/m2) between 2007 and 2012. Pre- and postoperative ROM, Knee Society scores, perioperative factors, complications and reoperations were compared.Results
UKA patients had higher preoperative ROM, and Knee Society pain (KSP), functional (KSF), and clinical (KSC) scores (p < 0.001, p = 0.0008, p = 0.0003, p = 0.051 respectively). Mean tourniquet times, operative times, and lengths of stay were lower after UKA. Four TKA patients required transfusion. Mean follow-up was 2.3 years. The frequency of manipulation under anesthesia was higher in TKA patients (p < 0.001), while the rate of component revision was similar between the two groups (1.2% vs. 1.7%, p = 0.328). Frequency of deep infection was lower in the UKA group (p = 0.016). Postoperative KSF, change in KSF, and ROM were higher (p < 0.0001) after UKA, but KSP and KSC were equivalent.Conclusions
Severely obese patients who underwent medial UKA demonstrated equal survivorship with substantially fewer reoperations, reduced deep infection, and less perioperative complications at short term follow-up. Severely obese patients had improved KSF scores and maintenance of ROM after UKA compared with TKA. 相似文献68.
69.
Mansouri D Mrad K Sassi S Driss-Fourati M Abbes I Koubaa-Mahjoub W Hechiche M Ben Romdhane K 《Annales de pathologie》2004,24(2):179-182
Pseudo-angiomatous hyperplasia of mammary stroma (PASH) is a histopathological entity which is a microscopic fortuitous finding in mammary biopsies performed for different reasons. It may be symptomatic and appears then as a palpable lump. The term pseudo-angiomatous emphasizes the characteristic aspect of the stroma simulating a vascular tumor. We report a case of PASH in a 71 year-old woman who presented a recurring breast mass with rapid swelling of the mammary gland (70 x 60 x 20 cm) treated by mastectomy. PASH must be distinguished from a well-differentiated angiosarcoma. It is ruled out by immunohistochemistry. 相似文献
70.
The numbers of referrals to genetics clinics for people with a family history of cancer is increasing rapidly. Although it is likely that presymptomatic testing will soon be available for some families, for the majority of people with a family history of malignancy, risk can only be assessed by examining their pedigrees and referring to standard texts. In order to find out if clinical geneticists are providing consistent risks and suggestions for management we surveyed consultant clinical geneticists with a questionnaire about four people with a family history of malignancy. The clinical geneticists replying to our questionnaire gave consistent advice for the person with a family history of colon cancer, but there was wide variation in suggested risks and management for those with family histories of breast and multisite cancers. This survey shows that deciding on appropriate management for cancer families can be difficult and that there is uncertainty about the most effective methods of screening young people at high risk of developing cancers. However, it is important to provide consistent advice in order to evaluate screening protocols and lack of consistency in advice given to different family members can cause anxiety and distress. Consistency may be achieved by the use of one model for risk calculation, and by representatives from several specialties, such as surgery, radiology, genetics, and public health working together in order to coordinate local and national screening policies. 相似文献