全文获取类型
收费全文 | 1026篇 |
免费 | 84篇 |
国内免费 | 26篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 76篇 |
妇产科学 | 10篇 |
基础医学 | 133篇 |
口腔科学 | 9篇 |
临床医学 | 113篇 |
内科学 | 210篇 |
皮肤病学 | 8篇 |
神经病学 | 81篇 |
特种医学 | 131篇 |
外科学 | 101篇 |
综合类 | 33篇 |
预防医学 | 77篇 |
眼科学 | 31篇 |
药学 | 76篇 |
肿瘤学 | 46篇 |
出版年
2023年 | 6篇 |
2022年 | 6篇 |
2021年 | 13篇 |
2020年 | 10篇 |
2019年 | 19篇 |
2018年 | 21篇 |
2017年 | 10篇 |
2016年 | 6篇 |
2015年 | 24篇 |
2014年 | 21篇 |
2013年 | 32篇 |
2012年 | 34篇 |
2011年 | 37篇 |
2010年 | 24篇 |
2009年 | 33篇 |
2008年 | 46篇 |
2007年 | 55篇 |
2006年 | 62篇 |
2005年 | 33篇 |
2004年 | 32篇 |
2003年 | 28篇 |
2002年 | 30篇 |
2001年 | 34篇 |
2000年 | 26篇 |
1999年 | 22篇 |
1998年 | 43篇 |
1997年 | 25篇 |
1996年 | 31篇 |
1995年 | 27篇 |
1994年 | 22篇 |
1993年 | 28篇 |
1992年 | 14篇 |
1991年 | 22篇 |
1990年 | 27篇 |
1989年 | 22篇 |
1988年 | 22篇 |
1987年 | 14篇 |
1986年 | 24篇 |
1985年 | 21篇 |
1984年 | 20篇 |
1983年 | 14篇 |
1982年 | 9篇 |
1981年 | 12篇 |
1980年 | 17篇 |
1979年 | 8篇 |
1978年 | 7篇 |
1977年 | 11篇 |
1976年 | 7篇 |
1975年 | 5篇 |
1972年 | 5篇 |
排序方式: 共有1136条查询结果,搜索用时 865 毫秒
21.
E5531, a synthetic non-toxic lipid A derivative blocks the immunobiological activities of lipopolysaccharide. 总被引:6,自引:0,他引:6
T Kawata J R Bristol D P Rossignol J R Rose S Kobayashi H Yokohama A Ishibashi W J Christ K Katayama I Yamatsu Y Kishi 《British journal of pharmacology》1999,127(4):853-862
1. The major pathological responses to Gram-negative bacterial sepsis are triggered by endotoxin or lipopolysaccharide. As endotoxin is shed from the bacterial outer membrane, it induces immunological responses that lead to release of a variety of cytokines and other cellular mediators. As part of a program aimed at developing a therapeutic agent for septic shock, we have developed E5531, a novel synthetic lipopolysaccharide antagonist. 2. As measured by release by tumour necrosis factor-alpha, human monocytes or whole blood can be activated by lipopolysaccharide, lipid A, and lipoteichoic acid (from Gram-positive bacteria). E5531 potently antagonizes activation by all these agents while itself being devoid of agonistic activity. 3. The inhibitory activity of E5531 was dependent on time of addition. When 10 nM E5531 was added simultaneously with lipopolysaccharide or 1 - 3 h before addition of lipopolysaccharide, production of tumour necrosis factor-alpha was inhibited by more than 98%. The addition of E5531 1 h after lipopolysaccharide reduced the efficacy of E5531 by 47%. 4. Antagonistic activity of E5531 was specific for lipopolysaccharide as it was ineffective at inhibiting interferon-gamma mediated NO release of RAW 264.7 cells, phorbor 12-myristate 13-acetate stimulated superoxide anion production in human neutrophils, concanavalin A stimulated mitogenic activity in murine thymocytes and tumor necrosis factor-alpha induced E-selectin expression in human umbilical vein endothelial cells. 5. E5531 as well as MY4, an anti-CD14 antibody, inhibited radiolabelled lipopolysaccharide binding in human monocytes. 6. These results support our contention that E5531 is a potent antagonist of lipopolysaccharide-induced release of tumour necrosis factor-alpha and other cellular mediators and may be an effective therapeutic agent for human septic shock due to Gram-negative bacteria. 相似文献
22.
The objective of this study was to evaluate whether certain foods and beverages that are high in sugar content or taste sweet are related to the prevalence and severity of the premenstrual syndrome. Specifically, we sought to evaluate whether consumption of "junk foods", chocolate, caffeine-free cola, fruit juices or alcoholic beverages might exert an effect on the premenstrual syndrome apart from any effects of daily consumption of beverages that are high in caffeine (caffeine-containing coffee, tea and colas). The study was based on 853 responses to a questionnaire probing menstrual and premenstrual health and certain daily dietary practices; it was mailed to female university students in Oregon. An analysis of the data revealed that the consumption of chocolate, but not of other junk foods, was related to the prevalence of the premenstrual syndrome among women with more severe premenstrual symptoms. Likewise, the consumption of alcoholic beverages (all alcoholic beverages and beer only) was related to the prevalence of the premenstrual syndrome among women with more severe symptoms, as were both fruit juice and caffeine-free soda. None of the associations was substantially altered when the daily consumption of beverages high in caffeine content was controlled for. Taken together, these data suggest that the consumption of foods and beverages that are high in sugar content or taste sweet is associated with prevalence of the premenstrual syndrome. 相似文献
23.
Nocturnal blood pressure and 24-hour pulse pressure are potent indicators of mortality in hemodialysis patients 总被引:11,自引:0,他引:11
Amar J Vernier I Rossignol E Bongard V Arnaud C Conte JJ Salvador M Chamontin B 《Kidney international》2000,57(6):2485-2491
BACKGROUND: Cardiovascular (CV) complications are the leading cause of mortality in hemodialysis patients. The role of arterial hypertension on the prognosis of CV in hemodialysis patients is not as clear as in the general population. The purpose of this study was to investigate the prognostic role of ambulatory blood pressure (BP) on CV mortality in treated hypertensive hemodialysis patients. METHODS: Fifty-seven treated hypertensive hemodialysis patients (56.87 +/- 16.22 years, 30 men) were prospectively studied. All patients initially underwent an ambulatory BP monitoring between two dialysis sessions. The outcome event studied was CV death; kidney transplantation and deaths not related to CV disease were censored. RESULTS: The duration of follow-up was 34.4 +/- 20.39 months, during which 10 CV and 8 non-CV fatal events occurred. In the 10 patients who died from CV complications, age, previous CV events, ambulatory systolic BP, ambulatory pulse pressure (PP), and life-long smoking level were significantly higher, and the office diastolic BP was lower at the time of inclusion than in those who did not die from CV complications (N = 47). Based on Cox analysis and after adjustment for age, sex, and previous CV events, a low office diastolic BP [relative risk (RR) 0.49, 95% CI, 0.25 to 0.93, P = 0.03], an elevated 24-hour PP (RR 1.85, 95% CI, 1.28 to 2.65, P = 0.009), and an elevated nocturnal systolic BP (RR 1.41, 95% CI, 1.08 to 1.84, P = 0.01) were predictors of CV mortality (RR associated with a 10 mm Hg increase in BP and in PP). CONCLUSION: This study demonstrates that nocturnal BP and 24-hour PP are independent predictors of CV mortality in treated hypertensive hemodialysis patients. Randomized trials are needed to investigate whether nocturnal BP and 24-hour PP are superior to office BP as targets for antihypertensive therapy in this high-risk group. 相似文献
24.
Parental awareness of risk factors for sudden infant death syndrome (SIDS) and infant care practices were compared in an area of relative deprivation and one of relative affluence in Cardiff. Awareness was high in both areas. More infants slept on the side in the deprived area (p < 0.02). One in three babies was exposed to cigarette smoking, significantly more in the deprived area (p < 0.001). Health professionals should discourage side sleeping and smoking, especially in areas of deprivation. 相似文献
25.
As a consequence of inhibition of the hepatic cytochrome P450 3A4 isozyme, treatment with HIV protease inhibitors can result in significant drug?drug interactions. One noteworthy interaction is between protease inhibitors and inhaled or intranasal corticosteroids. This interaction can result in adrenal insufficiency and iatrogenic Cushing's syndrome (with symptoms such as rapid weight gain, obesity, facial hirsutism and swelling), as well as hypertension, osteoporosis and decreased CD4 cell count. In this paper, we review and unite pharmacokinetic data, case reports and current research regarding this drug?drug interaction in order to suggest options for the clinical management of HIV‐positive patients requiring treatment with protease inhibitors and inhaled or intranasal corticosteroids. 相似文献
26.
27.
Dai Wangde Amoedo Nivea Dias Perry Justin Le Grand Bruno Boucard Aurelie Carreno Juan Zhao Lifu Brown David A. Rossignol Rodrigue Kloner Robert A. 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2022,36(2):217-227
Cardiovascular Drugs and Therapy - The present study was to determine whether OP2113 could limit myocardial infarction size and the no-reflow phenomenon in a rat myocardial ischemia/reperfusion... 相似文献
28.
29.
De Novo Mutations in the Motor Domain of KIF1A Cause Cognitive Impairment,Spastic Paraparesis,Axonal Neuropathy,and Cerebellar Atrophy
下载免费PDF全文
![点击此处可从《Human mutation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Jae‐Ran Lee Myriam Srour Doyoun Kim Fadi. F. Hamdan So‐Hee Lim Catherine Brunel‐Guitton Jean‐Claude Décarie Elsa Rossignol Grant A. Mitchell Allison Schreiber Rocio Moran Keith Van Haren Randal Richardson Joost Nicolai Karin M.E.J. Oberndorff Justin D. Wagner Kym M. Boycott Elisa Rahikkala Nella Junna Henna Tyynismaa Inge Cuppen Nienke E. Verbeek Connie T.R.M. Stumpel Michel A. Willemsen Sonja A. de Munnik Guy A. Rouleau Eunjoon Kim Erik‐Jan Kamsteeg Tjitske Kleefstra Jacques L. Michaud 《Human mutation》2015,36(1):69-78
KIF1A is a neuron‐specific motor protein that plays important roles in cargo transport along neurites. Recessive mutations in KIF1A were previously described in families with spastic paraparesis or sensory and autonomic neuropathy type‐2. Here, we report 11 heterozygous de novo missense mutations (p.S58L, p.T99M, p.G102D, p.V144F, p.R167C, p.A202P, p.S215R, p.R216P, p.L249Q, p.E253K, and p.R316W) in KIF1A in 14 individuals, including two monozygotic twins. Two mutations (p.T99M and p.E253K) were recurrent, each being found in unrelated cases. All these de novo mutations are located in the motor domain (MD) of KIF1A. Structural modeling revealed that they alter conserved residues that are critical for the structure and function of the MD. Transfection studies suggested that at least five of these mutations affect the transport of the MD along axons. Individuals with de novo mutations in KIF1A display a phenotype characterized by cognitive impairment and variable presence of cerebellar atrophy, spastic paraparesis, optic nerve atrophy, peripheral neuropathy, and epilepsy. Our findings thus indicate that de novo missense mutations in the MD of KIF1A cause a phenotype that overlaps with, while being more severe, than that associated with recessive mutations in the same gene. 相似文献
30.
A Gain‐of‐Function Mutation in NALCN in a Child with Intellectual Disability,Ataxia, and Arthrogryposis
下载免费PDF全文
![点击此处可从《Human mutation》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Kyota Aoyagi Elsa Rossignol Fadi F. Hamdan Ben Mulcahy Lin Xie Shinya Nagamatsu Guy A. Rouleau Mei Zhen Jacques L. Michaud 《Human mutation》2015,36(8):753-757
NALCN and its homologues code for the ion channel responsible for half of background Na+‐leak conductance in vertebrate and invertebrate neurons. Recessive mutations in human NALCN cause intellectual disability (ID) with hypotonia. Here, we report a de novo heterozygous mutation in NALCN affecting a conserved residue (p.R1181Q) in a girl with ID, episodic and persistent ataxia, and arthrogryposis. Interestingly, her episodes of ataxia were abolished by the administration of acetazolamide, similar to the response observed in episodic ataxia associated with other ion channels. Introducing the analogous mutation in the Caenorhabditis elegans homologue nca‐1 induced a coiling locomotion phenotype, identical to that obtained with previously characterized C. elegans gain‐of‐function nca alleles, suggesting that p.R1181Q confers the same property to NALCN. This observation thus suggests that dominant mutations in NALCN can cause a neurodevelopmental phenotype that overlaps with, while being mostly distinct from that associated with recessive mutations in the same gene. 相似文献