全文获取类型
收费全文 | 2234篇 |
免费 | 120篇 |
国内免费 | 32篇 |
专业分类
耳鼻咽喉 | 10篇 |
儿科学 | 82篇 |
妇产科学 | 37篇 |
基础医学 | 264篇 |
口腔科学 | 39篇 |
临床医学 | 162篇 |
内科学 | 467篇 |
皮肤病学 | 54篇 |
神经病学 | 91篇 |
特种医学 | 176篇 |
外科学 | 265篇 |
综合类 | 133篇 |
预防医学 | 128篇 |
眼科学 | 138篇 |
药学 | 175篇 |
中国医学 | 6篇 |
肿瘤学 | 159篇 |
出版年
2022年 | 30篇 |
2021年 | 57篇 |
2020年 | 20篇 |
2019年 | 37篇 |
2018年 | 39篇 |
2017年 | 32篇 |
2016年 | 43篇 |
2015年 | 58篇 |
2014年 | 74篇 |
2013年 | 112篇 |
2012年 | 127篇 |
2011年 | 139篇 |
2010年 | 89篇 |
2009年 | 73篇 |
2008年 | 113篇 |
2007年 | 136篇 |
2006年 | 115篇 |
2005年 | 115篇 |
2004年 | 77篇 |
2003年 | 87篇 |
2002年 | 73篇 |
2001年 | 64篇 |
2000年 | 53篇 |
1999年 | 53篇 |
1998年 | 46篇 |
1997年 | 38篇 |
1996年 | 32篇 |
1995年 | 31篇 |
1994年 | 23篇 |
1993年 | 24篇 |
1992年 | 23篇 |
1991年 | 19篇 |
1990年 | 19篇 |
1989年 | 35篇 |
1988年 | 23篇 |
1987年 | 26篇 |
1986年 | 31篇 |
1985年 | 19篇 |
1984年 | 20篇 |
1983年 | 17篇 |
1982年 | 12篇 |
1981年 | 13篇 |
1980年 | 12篇 |
1978年 | 10篇 |
1977年 | 8篇 |
1975年 | 15篇 |
1974年 | 7篇 |
1973年 | 9篇 |
1972年 | 15篇 |
1971年 | 7篇 |
排序方式: 共有2386条查询结果,搜索用时 296 毫秒
61.
Coakley G; Mok CC; Hajeer AH; Ollier WE; Turner D; Sinnott PJ; Hutchinson IV; Panayi GS; Lanchbury JS 《Rheumatology (Oxford, England)》1998,37(9):988-991
OBJECTIVE: To examine whether promoter polymorphisms associated with
variation in interleukin-10 (IL-10) production are relevant to the
development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS:
DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The
promoter region between -533 and - 1120 was amplified by polymerase chain
reaction, and polymorphisms detected by restriction enzyme digest or
sequence-specific oligonucleotide probing. RESULTS: We found no significant
difference in allele or haplotype frequencies between the groups.
CONCLUSION: There is no association between FS or RA and these recently
identified IL-10 promoter polymorphisms. Other genetic or environmental
factors could explain the alterations in IL-10 levels seen in these
conditions.
相似文献
62.
Angiotensin II (AII) action is coupled to the hydrolysis of phospholipids resulting in the formation of arachidonic acid, the precursor of both prostaglandins, and hydroxyeicosatetraenoic acids (HETEs). Since 12-HETE is not only a major arachidonate lipoxygenase (LO) product in the kidney, but is also a potent inhibitor of renin release, we studied the role of AII on renin inhibition and 12-HETE formation using rat renal cortical slices and isolated juxtaglomerular-like cells. In both preparations, 12-HETE was produced in a basal state. AII significantly inhibited renin release (control 100 +/- 3%, AII (10(8) M) 79 + 4%, P less than 0.01) and stimulated 12-HETE formation in slices (control 106 +/- 6%, AII 10(-8) M 177 +/- 18%, P less than 0.01) and in an enriched juxtaglomular cell preparation (control 96 +/- 3%, AII 10(-8) M 130 +/- 6%, P less than 0.001). A specific cyclooxygenase blocker, meclofenomate, or 5-LO blocker, U60,257, did not alter basal or AII-induced renin inhibition or 12-HETE formation by slices. The LO blockers BW755c, at 10(-5) M, or baicalein, 10(-6) M, did not significantly alter basal renin or 12-HETE levels, but BW755c at 10(-4) M, significantly stimulated basal renin (131 +/- 4%) and decreased basal 12-HETE levels (72 +/- 5%). However, both BW755c and baicalein blunted AII-induced renin inhibition (AII, 10(-8) M 70 +/- 3%, AII + BW755c, 10(-5) M 85 +/- 4%, P less than 0.02, AII + baicalein, 10(-6) M, 90 +/- 4%, P less than 0.005) and AII mediated 12-HETE formation (AII, 10(-8) M 150 +/- 5%, AII + BW755c, 10(-5) M 117 +/- 8%, P less than 0.02, AII + baicalein, 10(-6) M 110 +/- 3%, P less than 0.005). These results suggest that AII inhibition of renin is not mediated by the cyclooxygenase or 5-LO pathway, but rather by the 12-LO pathway. These findings reveal a new action for 12-LO products which may play a pivotal role in stimulus secretion coupling of renin secretion. 相似文献
63.
Babu GJ Zheng Z Natarajan P Wheeler D Janssen PM Periasamy M 《Cardiovascular research》2005,65(1):177-186
OBJECTIVE: Sarcolipin (SLN) is a novel 31-amino-acid protein associated with the sarcoplasmic reticulum (SR) whose function in cardiac muscle is poorly defined. In this study, we tested the hypothesis that SLN is a regulator of SR Ca(2+) transport function by overexpressing SLN in adult rat ventricular myocytes which express low levels of SLN. METHODS: Expression of SLN mRNA in rat tissues was analyzed by Northern blot as well by RT-PCR analysis. To define the role of SLN in cardiac muscle contractility, we overexpressed SLN in adult rat ventricular myocytes using adenoviral gene transfer techniques. Localization of SLN in the adult rat ventricular myocytes was determined using confocal microscopy. Myocyte contractility and calcium transients were measured using edge detection and Fura 2AM. RESULTS: Our results demonstrate that overexpression of SLN decreased the cell shortening significantly when compared to control myocytes, whereas the time to peak contraction was not altered. In addition, SLN overexpression prolonged the time of 50% relaxation. Calcium transient analysis shows that time to 50% decay of [Ca(2+) ]i was markedly prolonged in SLN-overexpressing myocytes (control -245.0+/-3.78 vs. SLN -199.0+/-3.25 ms, p<0.001). However, there were no significant differences in peak amplitudes of [Ca(2+)](i) between SLN-overexpressing and control myocytes. We further demonstrate that SLN is localized within the SR membrane similar to PLB and SR Ca(2+) ATPase. Co-immunoprecipitation studies indicate that SLN can physically interact with phospholamban. CONCLUSIONS: We conclude that SLN may play an important role in regulating the SR calcium ATPase pump, possibly by interacting with phospholamban. 相似文献
64.
Sakata Y Chancey AL Divakaran VG Sekiguchi K Sivasubramanian N Mann DL 《Basic research in cardiology》2008,103(1):60-68
The mechanisms that are responsible for the development of myocardial fibrosis in inflammatory cardiomyopathy are unknown.
We have previously generated lines of transgenic mice with cardiac-restricted overexpression of tumor necrosis factor (MHCsTNF
mice), a pro-inflammatory cytokine. The MHCsTNF mice develop a heart failure phenotype that is characterized by progressive
myocardial fibrosis, as well as increased levels transforming growth factor-β (TGF-β)(mRNA and protein. In order to determine
whether TGF-β-mediated signaling was responsible for the myocardial fibrosis observed in the MHCsTNF mice, we treated MHCsTNF
and littermate control mice from 4 to 12 weeks of age with a novel orally available TGF-β receptor antagonist (NP-40208).
At the time of terminal study, myocardial collagen content was determined using the picrosirius red technique, and left ventricular
(LV) systolic and diastolic function were determined using the Langendorff method. Treatment with NP-40208 resulted in a significant
(P < 0.05) 65% decrease in nuclear translocation of Smad 2/3, a significant (P < 0.05), decrease in the heart-weight to body-weight ratio from 6.5 to 5.7, a ∼37% decrease in fibrillar collagen content
(P < 0.01) and a significant (P < 0.05) decrease in the LV chamber stiffness by ∼25% in the MHCsTNF mice when compared to diluent-treated controls. Treatment
with NP-40208 had no discernable effect on LV systolic function, nor any effect on cardiac myocyte size or fetal gene expression
in the MHCsTNF mice. Taken together, these observations suggest that sustained pro-inflammatory signaling in the adult heart
is associated with a pro-fibrotic phenotype that arises, at least in part, from TGF-β-mediated signaling, with resultant activation
of Smad 2/3, leading to increased myocardial fibrosis and increased LV diastolic chamber stiffness.
Returned for 1. revision: 29 August 2007 1. Revision received: 24 September 2007 相似文献
65.
66.
Effects of electroacupuncture on gastric mucosal blood flow and transmucosal potential difference in stress rats 总被引:9,自引:0,他引:9
EfectsofelectroacupunctureongastricmucosalbloodflowandtransmucosalpotentialdiferenceinstressratsXUGuanSun1,SUNYong1,WANGZhe... 相似文献
67.
William R. Morgenlander Stephanie N. Henson Daniel R. Monaco Athena Chen Kirsten Littlefield Evan M. Bloch Eric Fujimura Ingo Ruczinski Andrew R. Crowley Harini Natarajan Savannah E. Butler Joshua A. Weiner Mamie Z. Li Tania S. Bonny Sarah E. Benner Ashwin Balagopal David Sullivan Shmuel Shoham Thomas C. Quinn Susan H. Eshleman Arturo Casadevall Andrew D. Redd Oliver Laeyendecker Margaret E. Ackerman Andrew Pekosz Stephen J. Elledge Matthew Robinson Aaron A.R. Tobian H. Benjamin Larman 《The Journal of clinical investigation》2021,131(7)
SARS-CoV-2 (CoV2) antibody therapies, including COVID-19 convalescent plasma (CCP), monoclonal antibodies, and hyperimmune globulin, are among the leading treatments for individuals with early COVID-19 infection. The functionality of convalescent plasma varies greatly, but the association of antibody epitope specificities with plasma functionality remains uncharacterized. We assessed antibody functionality and reactivities to peptides across the CoV2 and the 4 endemic human coronavirus (HCoV) genomes in 126 CCP donations. We found strong correlation between plasma functionality and polyclonal antibody targeting of CoV2 spike protein peptides. Antibody reactivity to many HCoV spike peptides also displayed strong correlation with plasma functionality, including pan-coronavirus cross-reactive epitopes located in a conserved region of the fusion peptide. After accounting for antibody cross-reactivity, we identified an association between greater alphacoronavirus NL63 antibody responses and development of highly neutralizing antibodies against CoV2. We also found that plasma preferentially reactive to the CoV2 spike receptor binding domain (RBD), versus the betacoronavirus HKU1 RBD, had higher neutralizing titer. Finally, we developed a 2-peptide serosignature that identifies plasma donations with high anti-spike titer, but that suffer from low neutralizing activity. These results suggest that analysis of coronavirus antibody fine specificities may be useful for selecting desired therapeutics and understanding the complex immune responses elicited by CoV2 infection. 相似文献
68.
69.
Type 2 diabetes is associated with significantly accelerated rates of macrovascular complications such as atherosclerosis. Emerging evidence now indicates that atherosclerosis is an inflammatory disease and that certain inflammatory markers may be key predictors of diabetic atherosclerosis. Proinflammatory cytokines and cellular adhesion molecules expressed by vascular and blood cells during stimulation by growth factors and cytokines seem to play major roles in the pathophysiology of atherosclerosis and diabetic vascular complications. However, more recently, data suggest that inflammatory responses can also be elicited by smaller oxidized lipids that are components of atherogenic oxidized low-density lipoprotein or products of phospholipase activation and arachidonic acid metabolism. These include oxidized lipids of the lipoxygenase and cyclooxygenase pathways of arachidonic acid and linoleic acid metabolism. These lipids have potent growth, vasoactive, chemotactic, oxidative, and proinflammatory properties in vascular smooth muscle cells, endothelial cells, and monocytes. Cellular and animal models indicate that these enzymes are induced under diabetic conditions, have proatherogenic effects, and also mediate the actions of growth factors and cytokines. This review highlights the roles of the inflammatory cyclooxygenase and 12/15-lipoxygenase pathways in the pathogenesis of diabetic vascular disease. Evidence suggests that inflammatory responses in the vasculature can be elicited by small oxidized lipids that are components of oxidized low-density lipoprotein or products of the lipoxygenase and cyclooxygenase pathways of arachidonic and linoleic acid metabolism. This review evaluates these inflammatory and proatherogenic pathways in the pathogenesis of diabetic vascular disease. 相似文献
70.