全文获取类型
收费全文 | 2254篇 |
免费 | 157篇 |
国内免费 | 4篇 |
专业分类
耳鼻咽喉 | 70篇 |
儿科学 | 96篇 |
妇产科学 | 39篇 |
基础医学 | 256篇 |
口腔科学 | 78篇 |
临床医学 | 196篇 |
内科学 | 478篇 |
皮肤病学 | 31篇 |
神经病学 | 187篇 |
特种医学 | 427篇 |
外国民族医学 | 1篇 |
外科学 | 216篇 |
综合类 | 47篇 |
一般理论 | 1篇 |
预防医学 | 63篇 |
眼科学 | 12篇 |
药学 | 101篇 |
1篇 | |
肿瘤学 | 115篇 |
出版年
2021年 | 16篇 |
2019年 | 17篇 |
2018年 | 23篇 |
2017年 | 24篇 |
2016年 | 18篇 |
2015年 | 27篇 |
2014年 | 47篇 |
2013年 | 58篇 |
2012年 | 71篇 |
2011年 | 61篇 |
2010年 | 63篇 |
2009年 | 75篇 |
2008年 | 62篇 |
2007年 | 77篇 |
2006年 | 85篇 |
2005年 | 64篇 |
2004年 | 54篇 |
2003年 | 58篇 |
2002年 | 40篇 |
2001年 | 49篇 |
2000年 | 37篇 |
1999年 | 52篇 |
1998年 | 88篇 |
1997年 | 92篇 |
1996年 | 93篇 |
1995年 | 80篇 |
1994年 | 44篇 |
1993年 | 70篇 |
1992年 | 19篇 |
1991年 | 25篇 |
1990年 | 35篇 |
1989年 | 61篇 |
1988年 | 48篇 |
1987年 | 56篇 |
1986年 | 61篇 |
1985年 | 82篇 |
1984年 | 44篇 |
1983年 | 35篇 |
1982年 | 33篇 |
1981年 | 35篇 |
1980年 | 44篇 |
1979年 | 15篇 |
1978年 | 30篇 |
1977年 | 35篇 |
1976年 | 33篇 |
1975年 | 38篇 |
1974年 | 20篇 |
1973年 | 16篇 |
1970年 | 16篇 |
1968年 | 14篇 |
排序方式: 共有2415条查询结果,搜索用时 15 毫秒
91.
92.
93.
Li YW Hill G Wong H Kelly N Ward K Pierdomenico M Ren S Gilligan P Grossman S Trainor G Taub R McElroy J Zazcek R 《The Journal of pharmacology and experimental therapeutics》2003,305(1):86-96
4-(1,3-Dimethoxyprop-2-ylamine)-2,7-dimethyl-8-(2,4-dichlorophenyl)-pyrazolo[1,5-a]-1,3,5-triazine (DMP696) is a highly selective and potent, nonpeptide corticotropin-releasing factor 1 (CRF(1)) antagonist. In this study, we measured in vivo CRF(1) receptor occupancy of DMP696 by using ex vivo ligand binding and quantitative autoradiography and explored the relationship of receptor occupancy with plasma and brain exposure and behavioral efficacy. In vitro affinity (IC(50)) of DMP696 to brain CRF(1) receptors measured using the brain section binding autoradiography in this study is similar to that assessed using homogenized cell membrane assays previously. The ex vivo binding assay was validated by demonstrating that potential underestimation of receptor occupancy with this procedure could be minimized by identifying an appropriate in vitro incubation time (40 min) based upon the dissociation kinetics of DMP696. Orally administrated DMP696 dose dependently occupied CRF(1) receptors in the brain, with ~60% occupancy at 3 mg/kg. In the defensive withdrawal test of anxiety, this dose of DMP696 produced approximately 50% reduction in the exit latency. The time course of plasma and brain drug levels paralleled that of receptor occupancy, with peak exposure at 90 min after dosing. The plasma-free concentration of DMP696 corresponding to 50% CRF(1) receptor occupancy (in vivo IC(50), 1.22 nM) was similar to the in vitro IC(50) (~1.0 nM). Brain concentrations of DMP696 were over 150-fold higher than the plasma-free levels. In conclusion, doses of DMP696 occupying over 50% brain CRF(1) receptors are consistent with doses producing anxiolytic efficacy in the defense withdrawal test of anxiety, and the IC(50) value estimated in vivo based on plasma-free drug concentrations is consistent with the in vitro IC(50) value. 相似文献
94.
Abby C. Lee Grant Castaneda Wei Tse Li Chengyu Chen Neil Shende Jaideep Chakladar Pam R. Taub Eric Y. Chang Weg M. Ongkeko 《Viruses》2021,13(6)
Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19. 相似文献
95.
96.
Interleukin-4 (IL-4) is a potent mediator of growth and differentiation of cells of several hematopoietic lineages. Interleukin-5 (IL-5) is a lineage-specific hematopoietic growth factor that stimulates the production of eosinophils and eosinophil colonies from normal human bone marrow cells. By using somatic cell hybrids and in situ chromosomal hybridization, we localized the IL-4 and IL-5 genes to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, the IL-4 and IL-5 genes were found to be deleted in the 5q- chromosome of four patients with refractory anemia (RA) or therapy-related acute nonlymphocytic leukemia (t-ANLL), who had a del(5q). Thus a small segment of chromosome 5 contains IL-4, IL-5, IL- 3, and GM-CSF as well as other genes such as CD14 and EGR1. Our findings that each of these genes was deleted in the 5q- chromosome suggest that loss of function of one or more of these genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q). 相似文献
97.
Percutaneous transluminal coronary angioplasty in patients 70 years of age or older: 12 years' experience. 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《Heart (British Cardiac Society)》网站下载免费的PDF全文](/ch/ext_images/free.gif)
OBJECTIVE--To evaluate the short and long term results of coronary angioplasty in patients aged 70 years and older and identify the determinants of long-term survival. DESIGN--A retrospective analysis of clinical, angiographic, and procedure related variables on a consecutive series of patients. PATIENTS--163 patients aged 70 years and older (mean (range) age 73 (70-83) years; 63% men) who underwent a first coronary angioplasty procedure between 1981 and 1993. RESULTS--Procedural success was achieved in 82% of patients. Four patients (2%) died, three (2%) had a myocardial infarction, and five (3%) underwent emergency coronary artery bypass surgery. Complete follow up data were available for all patients (median (range) 35 (2-146) months). During the follow up period 16 patients (10%) died, two (1%) suffered non-fatal myocardial infarction, and 12 (7%) underwent elective coronary artery bypass surgery. A second angioplasty procedure was performed in 24 patients (15%). The cumulative probability of survival was 90.7% at 1 year and 83.4% at 5 years. Survival free from myocardial infarction, bypass surgery, and repeat angioplasty at 1 and 5 years was 68.2% and 56.0%, respectively. Proportional hazards regression analyses identified incomplete revascularisation as the only independent predictor of poorer overall survival (P = 0.04) and event free survival (P < 0.001). At census, of the 143 survivors, 75 (52%) were asymptomatic, 58 (41%) had mild angina, and only 10 (7%) complained of grade III or IV angina. Some 112 patients (78%) improved by at least two angina grades. CONCLUSION--Coronary angioplasty can be performed safely in the elderly and provides good symptomatic relief and favourable long-term outcome. Complete revascularisation may not be necessary if the primary goal is to achieve symptomatic relief, but incomplete revascularisation is associated with poorer long-term survival. 相似文献
98.
A five-drug remission induction regimen with intensive consolidation for adults with acute lymphoblastic leukemia: cancer and leukemia group B study 8811 总被引:23,自引:13,他引:23
Larson RA; Dodge RK; Burns CP; Lee EJ; Stone RM; Schulman P; Duggan D; Davey FR; Sobol RE; Frankel SR 《Blood》1995,85(8):2025-2037
The goal of this phase II multicenter clinical trial was to evaluate a new intensive chemotherapy program for adults with untreated acute lymphoblastic leukemia (ALL) and to examine prospectively the impact of clinical and biologic characteristics on the outcome. One hundred ninety-seven eligible and evaluable patients (16 to 80 years of age; median, 32 years of age) received cyclophosphamide, daunorubicin, vincristine, prednisone, and L-asparaginase; 167 patients (85%) achieved a complete remission (CR), 13 (7%) had refractory disease, and 17 (9%) died during induction. A higher CR rate was observed in younger patients (94% for those < 30 years old, 85% for those 30 to 59 years old, and 39% for those > or = 60 years old, P < .001) and in those who had a mediastinal mass (100%) or blasts with a T-cell immunophenotype. Eighty percent of B-lineage and 97% of T-cell ALL patients achieved a CR (P = .01). The coexpression of myeloid antigens did not affect the response rate or duration. Seventy percent of those with cytogenetic or molecular evidence of the Philadelphia (Ph) chromosome and 84% of those without such evidence achieved a CR (P = .11). Patients in remission received multiagent consolidation treatment, central nervous system prophylaxis, late intensification, and maintenance chemotherapy for a total of 24 months. After a median follow-up time of 43 months, the median survival for all 197 patients is 36 months; the median remission duration for the 167 CR patients is 29 months. Favorable pretreatment characteristics relative to remission duration or survival are younger age, the presence of a mediastinal mass or lymphadenopathy, a white blood cell count (WBC) less than 30,000/microL, L1 morphology, T or TMy immunophenotype, and the absence of the Ph chromosome. The estimates of the proportion surviving at 3 years are 69% for patients less than 30 years old, 39% for those 30 to 59 years old, 89% for those who had a mediastinal mass, 59% with WBC less than 30,000/microL, 63% with L1 morphology, 69% for T or TMy antigen expression, and 62% for those who lack the Ph chromosome. Fifteen patients (8%) had no unfavorable prognostic factors and have an estimated probability of survival at 5 years of 100% (95% confidence interval, 77% to 100%). This intensive chemotherapy regimen produces a high remission rate and a high proportion of durable remissions in adults with ALL. 相似文献
99.
Dvorak AM; Tepper RI; Weller PF; Morgan ES; Estrella P; Monahan-Earley RA; Galli SJ 《Blood》1994,83(12):3600-3612
We used light and electron microscopy to analyze the eyelid inflammation that develops in transgenic mice that overexpress interleukin-4 (IL-4; Tepper et al, Cell 62:457, 1990). Analysis of alkaline Giemsa-stained plastic sections examined by light microscopy (Dvorak et al, J Exp Med 132:558, 1970), as well as by routine transmission electron microscopy, indicated that the mast cells in the inflammatory eyelid lesions were undergoing piecemeal degranulation, a form of secretion in which the cells' cytoplasmic granules exhibit characteristic morphologic changes that are thought to be associated with the prolonged, vesicle-mediated release of the granules' constituents. Moreover, by using a newly reported enzyme affinity-gold method, which stains histamine based on binding to diamine oxidase-gold (Dvorak et al, J Histochem Cytochem 41:787, 1993), we show that these activated mast cells had released much of their histamine content. The eyelid lesions also exhibited increased numbers of mast cells; interstitial fibrosis, particularly around cutaneous nerves and blood vessels; activated fibroblasts; focal axonal damage; venules with endothelial cells containing numerous vesiculo-vacuolar organelles; and infiltrates of neutrophils and eosinophils. Our findings illustrate that overexpression of the IL-4 gene in vivo can result in eyelid lesions associated with piecemeal degranulation of mast cells, as well as tissue fibrosis and a variety of other pathologic changes. These results also represent the first direct morphologic evidence for histamine secretion by mast cells in vivo. 相似文献
100.