全文获取类型
收费全文 | 3493篇 |
免费 | 235篇 |
国内免费 | 15篇 |
专业分类
耳鼻咽喉 | 81篇 |
儿科学 | 134篇 |
妇产科学 | 50篇 |
基础医学 | 423篇 |
口腔科学 | 35篇 |
临床医学 | 407篇 |
内科学 | 690篇 |
皮肤病学 | 83篇 |
神经病学 | 338篇 |
特种医学 | 407篇 |
外科学 | 329篇 |
综合类 | 120篇 |
一般理论 | 1篇 |
预防医学 | 313篇 |
眼科学 | 47篇 |
药学 | 137篇 |
中国医学 | 1篇 |
肿瘤学 | 147篇 |
出版年
2022年 | 28篇 |
2021年 | 68篇 |
2020年 | 39篇 |
2019年 | 49篇 |
2018年 | 72篇 |
2017年 | 41篇 |
2016年 | 50篇 |
2015年 | 57篇 |
2014年 | 87篇 |
2013年 | 131篇 |
2012年 | 124篇 |
2011年 | 133篇 |
2010年 | 120篇 |
2009年 | 99篇 |
2008年 | 136篇 |
2007年 | 131篇 |
2006年 | 127篇 |
2005年 | 123篇 |
2004年 | 118篇 |
2003年 | 111篇 |
2002年 | 106篇 |
2001年 | 93篇 |
2000年 | 73篇 |
1999年 | 80篇 |
1998年 | 119篇 |
1997年 | 97篇 |
1996年 | 94篇 |
1995年 | 71篇 |
1994年 | 72篇 |
1993年 | 75篇 |
1992年 | 60篇 |
1991年 | 42篇 |
1990年 | 66篇 |
1989年 | 74篇 |
1988年 | 55篇 |
1987年 | 80篇 |
1986年 | 61篇 |
1985年 | 76篇 |
1984年 | 53篇 |
1983年 | 32篇 |
1982年 | 41篇 |
1981年 | 35篇 |
1980年 | 38篇 |
1979年 | 28篇 |
1978年 | 28篇 |
1977年 | 26篇 |
1976年 | 29篇 |
1975年 | 28篇 |
1973年 | 19篇 |
1971年 | 18篇 |
排序方式: 共有3743条查询结果,搜索用时 93 毫秒
101.
MacDonald I; Wang H; Grand R; Armitage RJ; Fanslow WC; Gregory CD; Gordon J 《Blood》1996,87(3):1147-1154
Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma. 相似文献
102.
Moderation of hemophilia A phenotype by the factor V R506Q mutation 总被引:11,自引:1,他引:11
Nichols WC; Amano K; Cacheris PM; Figueiredo MS; Michaelides K; Schwaab R; Hoyer L; Kaufman RJ; Ginsburg D 《Blood》1996,88(4):1183-1187
Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency. 相似文献
103.
104.
Carolina Nazzal Steven Shea Cecilia Castro-Diehl Tania Alfaro Patricia Frenz Carlos J. Rodriguez 《Global Heart》2018,13(1):19-26
Background
Social determinants differ between countries, which is not always considered when adapting health policies and interventions to face inequalities in noncommunicable diseases and their risk factors.Objectives
The study sought to analyze educational inequalities in controlled blood pressure (CBP), obesity, and smoking in study populations from Chile and the United States in 2 periods, both countries with large social inequalities.Methods
The study used data from the first and fifth waves of the MESA (Multiethnic Study of Atherosclerosis) cohort, and the 2003 and 2009 to 2010 Chilean National Health Survey (CNHS) survey outcome measures. The study compared cardiovascular risk factors prevalence as well as relative index of inequality (RII) and slope index of inequality (SII) between the 2 samples.Results
In the CNHS 67.9% and 52.6% of participants had below primary education in 2003 and 2009 to 2010, respectively, compared with 12.3% and 8.1% in the first and fifth waves of the MESA study, respectively. Smoking prevalence was higher and increased in the CNHS compared with the MESA study, concentrated in better-educated women in both years (RII: 0.34; 95% confidence interval [CI]: 0.17 to 0.68; and RII: 0.55; 95% CI: 0.34 to 0.89, respectively). In contrast, smoking decreased over time in the MESA study in all socioeconomic strata, although relative inequalities increased in both sexes (for women, RII: 2.32; 95% CI 1.36 to 3.97; for men, RII: 3.34; 95% CI 2.04 to 5.47). CBP prevalence in both periods was higher in the first and fifth waves of the MESA study (69.7% and 80.2%) compared with the 2003 and 2009 to 2010 CNHS samples (34.2% and 52.3%), but only for the MESA study RII, favoring the better educated, was it significant in both periods and sexes. Obesity inequalities for Chilean women decreased slightly between 2003 and 2009 as prevalence grew in the most educated (RII: 2.21 to 1.68; SII: 0.29 to 0.22, respectively); conversely, they increased for both sexes in the MESA study.Conclusions
The study findings confirm that patterns and trends in prevalence, and absolute and relative inequalities vary by country, suggesting that context and cultural issues matters. 相似文献105.
Assessment of aldehyde dehydrogenase in viable cells 总被引:3,自引:4,他引:3
Jones RJ; Barber JP; Vala MS; Collector MI; Kaufmann SH; Ludeman SM; Colvin OM; Hilton J 《Blood》1995,85(10):2742-2746
Cytosolic aldehyde dehydrogenase (ALDH), an enzyme responsible for oxidizing intracellular aldehydes, has an important role in ethanol, vitamin A, and cyclophosphamide metabolism. High expression of this enzyme in primitive stem cells from multiple tissues, including bone marrow and intestine, appears to be an important mechanism by which these cells are resistant to cyclophosphamide. However, although hematopoietic stem cells (HSC) express high levels of cytosolic ALDH, isolating viable HSC by their ALDH expression has not been possible because ALDH is an intracellular protein. We found that a fluorescent aldehyde, dansyl aminoacetaldehyde (DAAA), could be used in flow cytometry experiments to isolate viable mouse and human cells based on their ALDH content. The level of dansyl fluorescence exhibited by cells after incubation with DAAA paralleled cytosolic ALDH levels determined by Western blotting and the sensitivity of the cells to cyclophosphamide. Moreover, DAAA appeared to be a more sensitive means of assessing cytosolic ALDH levels than Western blotting. Bone marrow progenitors treated with DAAA proliferated normally. Furthermore, marrow cells expressing high levels of dansyl fluorescence after incubation with DAAA were enriched for hematopoietic progenitors. The ability to isolate viable cells that express high levels of cytosolic ALDH could be an important component of methodology for identifying and purifying HSC and for studying cyclophosphamide-resistant tumor cell populations. 相似文献
106.
Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults. 相似文献
107.
108.
Hoshino Y Koide H Furuya K Haberaecker WW Lee SH Kodama T Kanazawa H Oku N Shea KJ 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(1):33-38
Synthetic polymer nanoparticles (NPs) that bind venomous molecules and neutralize their function in vivo are of significant interest as "plastic antidotes." Recently, procedures to synthesize polymer NPs with affinity for target peptides have been reported. However, the performance of synthetic materials in vivo is a far greater challenge. Particle size, surface charge, and hydrophobicity affect not only the binding affinity and capacity to the target toxin but also the toxicity of NPs and the creation of a "corona" of proteins around NPs that can alter and or suppress the intended performance. Here, we report the design rationale of a plastic antidote for in vivo applications. Optimizing the choice and ratio of functional monomers incorporated in the NP maximized the binding affinity and capacity toward a target peptide. Biocompatibility tests of the NPs in vitro and in vivo revealed the importance of tuning surface charge and hydrophobicity to minimize NP toxicity and prevent aggregation induced by nonspecific interactions with plasma proteins. The toxin neutralization capacity of NPs in vivo showed a strong correlation with binding affinity and capacity in vitro. Furthermore, in vivo imaging experiments established the NPs accelerate clearance of the toxic peptide and eventually accumulate in macrophages in the liver. These results provide a platform to design plastic antidotes and reveal the potential and possible limitations of using synthetic polymer nanoparticles as plastic antidotes. 相似文献
109.
Yau JW Xie J Lamoureux E Klein R Klein BE Cotch MF Bertoni AG Shea S Wong TY 《Diabetes research and clinical practice》2012,95(2):265-274
Aim
To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.Methods
The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45-84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.Results
After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12-2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37-5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.Conclusion
Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways. 相似文献110.