全文获取类型
收费全文 | 1389篇 |
免费 | 116篇 |
国内免费 | 2篇 |
专业分类
耳鼻咽喉 | 8篇 |
儿科学 | 76篇 |
妇产科学 | 45篇 |
基础医学 | 208篇 |
口腔科学 | 8篇 |
临床医学 | 220篇 |
内科学 | 210篇 |
皮肤病学 | 32篇 |
神经病学 | 133篇 |
特种医学 | 10篇 |
外科学 | 127篇 |
综合类 | 32篇 |
一般理论 | 2篇 |
预防医学 | 186篇 |
眼科学 | 13篇 |
药学 | 91篇 |
中国医学 | 4篇 |
肿瘤学 | 102篇 |
出版年
2024年 | 2篇 |
2023年 | 21篇 |
2022年 | 10篇 |
2021年 | 40篇 |
2020年 | 23篇 |
2019年 | 48篇 |
2018年 | 38篇 |
2017年 | 32篇 |
2016年 | 48篇 |
2015年 | 44篇 |
2014年 | 49篇 |
2013年 | 95篇 |
2012年 | 113篇 |
2011年 | 109篇 |
2010年 | 68篇 |
2009年 | 54篇 |
2008年 | 75篇 |
2007年 | 86篇 |
2006年 | 96篇 |
2005年 | 61篇 |
2004年 | 87篇 |
2003年 | 82篇 |
2002年 | 66篇 |
2001年 | 6篇 |
1999年 | 13篇 |
1998年 | 16篇 |
1997年 | 11篇 |
1996年 | 17篇 |
1995年 | 7篇 |
1994年 | 15篇 |
1993年 | 4篇 |
1992年 | 8篇 |
1991年 | 4篇 |
1990年 | 2篇 |
1989年 | 4篇 |
1988年 | 2篇 |
1985年 | 2篇 |
1984年 | 3篇 |
1982年 | 9篇 |
1981年 | 10篇 |
1980年 | 5篇 |
1979年 | 3篇 |
1975年 | 3篇 |
1974年 | 3篇 |
1973年 | 2篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1968年 | 1篇 |
1964年 | 1篇 |
1933年 | 1篇 |
排序方式: 共有1507条查询结果,搜索用时 15 毫秒
41.
The Leishmania granuloma shares some, though not all, properties with that formed following mycobacterial infection. As a simplified, noncaseating granuloma composed of relatively few and largely mononuclear cell populations, it provides a tractable model system to investigate intra-granuloma cellular dynamics, immune regulation, and antimicrobial resistance. Here, the occurrence of granulomatous pathology across the spectrum of leishmaniasis, in humans and animal reservoir hosts, is first described. However, this review focuses on the process of hepatic granuloma formation as studied in rodent models of visceral leishmaniasis, starting from the initial infection of Kupffer cells to the involution of the granuloma after pathogen clearance. It describes how the application of intravital imaging and the use of computational modeling have changed some of our thoughts on granuloma function, and illustrates how host-directed therapies have been used to manipulate granuloma form and function for therapeutic benefit. Where appropriate, lessons that may be equally applicable across the spectrum of granulomatous diseases are highlighted. 相似文献
42.
Moore L Lu X Ghebranious N Tyner S Donehower LA 《Mechanisms of ageing and development》2007,128(11-12):717-730
Evidence has accumulated that p53, a prototypical tumor suppressor, may also influence aspects of organismal aging. We have previously described a p53 mutant mouse model, the p53+/m mouse, which is cancer resistant yet exhibits reduced longevity and premature aging phenotypes. p53+/m mice express one full length p53 allele and one truncated p53 allele that is translated into a C-terminal fragment of p53 termed the M protein. The augmented cancer resistance and premature aging phenotypes in the p53+/m mice are consistent with a hyperactive p53 state. To determine how the M protein could increase p53 activity, we examined the M protein in various cellular contexts. Here, we show that embryo fibroblasts from p53+/m mice exhibit reduced proliferation and cell cycle progression compared to embryo fibroblasts from p53+/- mice (with equivalent wild-type p53 dosage). The M protein interacts with wild-type p53, increases its stability, and facilitates its nuclear localization in the absence of stress. Despite increasing p53 stability, the M protein does not disrupt p53-Mdm2 interactions and does not prevent p53 ubiquitination. These results suggest molecular mechanisms by which the M protein could influence the aging and cancer resistance phenotypes in the p53+/m mouse. 相似文献
43.
Investigating the human immunodeficiency virus type 1-infected monocyte-derived macrophage secretome
Ciborowski P Kadiu I Rozek W Smith L Bernhardt K Fladseth M Ricardo-Dukelow M Gendelman HE 《Virology》2007,363(1):198-209
Mononuclear phagocytes (bone marrow monocyte-derived macrophages, alveolar macrophages, perivascular macrophages, and microglia) are reservoirs and vehicles of dissemination for the human immunodeficiency virus type-1 (HIV-1). How virus alters mononuclear phagocyte immunoregulatory activities to complete its life cycle and influence disease is incompletely understood. In attempts to better understanding the influence of virus on macrophage functions, we used one-dimensional electrophoresis, and liquid chromatography tandem mass spectrometry to analyze the secretome of HIV-1-infected human monocyte-derived macrophages. We identified 110 proteins in culture supernatants of control (uninfected) and virus-infected cells. Differentially expressed cytoskeletal, enzymes, redox, and immunoregulatory protein classes were discovered and validated by Western blot tests. These included, but were not limited to, cystatin C, cystatin B, chitinase 3-like 1 protein, cofilin-1, l-plastin, superoxide dismutase, leukotriene A(4) hydrolase, and alpha-enolase. This study, using a unique proteomics platform, provides novel insights into virus-host cell interactions that likely affect the functional role of macrophages in HIV disease. 相似文献
44.
Arginase and α‐smooth muscle actin induction after hyperoxic exposure in a mouse model of bronchopulmonary dysplasia 下载免费PDF全文
Jennifer K Trittmann Markus Velten Kathryn M Heyob Hanadi Almazroue Yi Jin Leif D Nelin Lynette K Rogers 《Clinical and experimental pharmacology & physiology》2018,45(6):556-562
The L‐arginine/NO pathway is an important regulator of pulmonary hypertension, the leading cause of mortality in patients with the chronic lung disease of prematurity, bronchopulmonary dysplasia. L‐arginine can be metabolized by NO synthase (NOS) to form L‐citrulline and NO, a potent vasodilator. Alternatively, L‐arginine can be metabolized by arginase to form urea and L‐ornithine, a precursor to collagen and proline formation important in vascular remodelling. In the current study, we hypothesized that C3H/HeN mice exposed to prolonged hyperoxia would have increased arginase expression and pulmonary vascular wall cell proliferation. C3H/HeN mice were exposed to 14 days of 85% O2 or room air and lung homogenates analyzed by western blot for protein levels of arginase I, arginase II, endothelial NOS (eNOS), ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and α‐smooth muscle actin (α‐SMA). Hyperoxia did not change arginase I or eNOS protein levels. However, arginase II protein levels were 15‐fold greater after hyperoxia exposure than in lungs exposed to room air. Greater protein levels of ODC and OAT were found in lungs following hyperoxic exposure than in room air animals. α‐SMA protein levels were found to be 7‐fold greater in the hyperoxia exposed lungs than in room air lungs. In the hyperoxia exposed lungs there was evidence of greater pulmonary vascular wall cell proliferation by α‐SMA immunohistochemistry than in room air lungs. Taken together, these data are consistent with a more proliferative vascular phenotype, and may explain the propensity of patients with bronchopulmonary dysplasia to develop pulmonary hypertension. 相似文献
45.
46.
J Christopher Gallagher Prachi S Jindal Lynette M Smith 《Journal of bone and mineral research》2014,29(1):173-181
There is limited information on the effects of vitamin D on serum 25 hydroxyvitamin D (25OHD) in young people and none on African Americans. The main objective of this trial was to measure the effect of different doses of vitamin D3 on serum 25OHD and serum parathyroid hormone (PTH) in young women with vitamin D insufficiency (serum 25OHD ≤ 20 ng/mL (50 nmol/L). A randomized double‐blind placebo‐controlled trial of vitamin D3 was conducted in young white and African American women, age 25 to 45 years. A total of 198 healthy white (60%) and African American (40%) women were randomly assigned to placebo, or to 400, 800, 1600, or 2400 IU of vitamin D3 daily. Calcium supplements were added to maintain a total calcium intake of 1000 to 1200 mg daily. The primary outcomes of the study were the final serum 25OHD and PTH levels at 12 months. The absolute increase in serum 25OHD with 400, 800, 1600, and 2400 IU of vitamin D daily was slightly greater in African American women than in white women. On the highest dose of 2400 IU/d, the mixed model predicted that mean 25OHD increased from baseline 12.4 ng/mL (95% confidence interval [CI], 9.2–15.7) to 43.2 ng/mL (95% CI, 38.2–48.1) in African American women and from 15.0 ng/mL (95% CI, 12.3–17.6) to 39.1 ng/mL (95% CI, 36.2–42.0) in white women. There was no significant effect of vitamin D dose on serum PTH in either race but there was a significant inverse relationship between final serum PTH and serum 25OHD. Serum 25OHD exceeded 20 ng/mL in 97.5% of whites on the 400 IU/d dose and between 800 and 1600 IU/d for African Americans. The recommended dietary allowance (RDA) suggested by the Institute of Medicine for young people is 600 IU daily. The increase in serum 25OHD after vitamin D supplementation was similar in young and old, and in white and African American women. © 2014 American Society for Bone and Mineral Research. 相似文献
47.
48.
Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice 下载免费PDF全文
Nicole L. Baganz Rebecca E. Horton Alfredo S. Calderon W. Anthony Owens Jaclyn L. Munn Lora T. Watts Nina Koldzic-Zivanovic Nathaniel A. Jeske Wouter Koek Glenn M. Toney Lynette C. Daws 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(48):18976-18981
Mood disorders cause much suffering and are the single greatest cause of lost productivity worldwide. Although multiple medications, along with behavioral therapies, have proven effective for some individuals, millions of people lack an effective therapeutic option. A common serotonin (5-HT) transporter (5-HTT/SERT, SLC6A4) polymorphism is believed to confer lower 5-HTT expression in vivo and elevates risk for multiple mood disorders including anxiety, alcoholism, and major depression. Importantly, this variant is also associated with reduced responsiveness to selective 5-HT reuptake inhibitor antidepressants. We hypothesized that a reduced antidepressant response in individuals with a constitutive reduction in 5-HTT expression could arise because of the compensatory expression of other genes that inactivate 5-HT in the brain. A functionally upregulated alternate transporter for 5-HT may prevent extracellular 5-HT from rising to levels sufficiently high enough to trigger the adaptive neurochemical events necessary for therapeutic benefit. Here we demonstrate that expression of the organic cation transporter type 3 (OCT3, SLC22A3), which also transports 5-HT, is upregulated in the brains of mice with constitutively reduced 5-HTT expression. Moreover, the OCT blocker decynium-22 diminishes 5-HT clearance and exerts antidepressant-like effects in these mice but not in WT animals. OCT3 may be an important transporter mediating serotonergic signaling when 5-HTT expression or function is compromised. 相似文献
49.
50.