全文获取类型
收费全文 | 503篇 |
免费 | 48篇 |
国内免费 | 5篇 |
专业分类
儿科学 | 28篇 |
妇产科学 | 2篇 |
基础医学 | 37篇 |
口腔科学 | 2篇 |
临床医学 | 52篇 |
内科学 | 146篇 |
皮肤病学 | 9篇 |
神经病学 | 19篇 |
特种医学 | 33篇 |
外科学 | 17篇 |
综合类 | 10篇 |
预防医学 | 47篇 |
药学 | 31篇 |
1篇 | |
肿瘤学 | 122篇 |
出版年
2021年 | 8篇 |
2020年 | 7篇 |
2019年 | 2篇 |
2018年 | 13篇 |
2017年 | 10篇 |
2016年 | 11篇 |
2015年 | 16篇 |
2014年 | 11篇 |
2013年 | 18篇 |
2012年 | 27篇 |
2011年 | 24篇 |
2010年 | 18篇 |
2009年 | 23篇 |
2008年 | 16篇 |
2007年 | 31篇 |
2006年 | 20篇 |
2005年 | 18篇 |
2004年 | 13篇 |
2003年 | 11篇 |
2002年 | 16篇 |
2001年 | 14篇 |
2000年 | 14篇 |
1999年 | 13篇 |
1998年 | 11篇 |
1997年 | 26篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 14篇 |
1993年 | 8篇 |
1992年 | 13篇 |
1991年 | 12篇 |
1990年 | 12篇 |
1989年 | 8篇 |
1988年 | 13篇 |
1987年 | 5篇 |
1986年 | 2篇 |
1985年 | 7篇 |
1984年 | 5篇 |
1983年 | 7篇 |
1982年 | 4篇 |
1981年 | 7篇 |
1980年 | 2篇 |
1977年 | 9篇 |
1976年 | 4篇 |
1974年 | 2篇 |
1972年 | 2篇 |
1966年 | 1篇 |
1964年 | 2篇 |
1963年 | 1篇 |
1943年 | 1篇 |
排序方式: 共有556条查询结果,搜索用时 31 毫秒
1.
Cytochrome P450IIE1 genetic polymorphisms, racial variation, and lung cancer risk. 总被引:10,自引:0,他引:10
S Kato P G Shields N E Caporaso R N Hoover B F Trump H Sugimura A Weston C C Harris 《Cancer research》1992,52(23):6712-6715
2.
Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones
下载免费PDF全文
![点击此处可从《Clinical and experimental immunology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma. 相似文献
3.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
4.
Bowman E Shields P Caporaso N Tucker M Hoover R Trump B Harris C 《Oncology reports》1997,4(2):269-272
A 193 base pair repeat polymorphism in the human poly(ADP-ribose) polymerase (PADPRP) pseudogene found on chromosome 13 has been associated with lung cancer, endemic Burkitt lymphoma, B-cell lymphoma, breast cancer and colorectal carcinoma. We investigated the frequency of the PADPRP genetic polymorphism in a hospital-based case-control study of lung cancer for 54 cases and 47 controls. There was a statistically significant difference in allelic frequency between Caucasians and African Americans (p<0.001). For African Americans, the odds ratio for lung cancer and the 'B' allele was 2.38 (95% C.I.=0.73, 7.69) and for Caucasians 0.44 (95% C.I.=0.11, 1.77). The results for the African Americans, however, were not in Hardy-Weinberg equilibrium, although the Caucasians were. Thus, this study, albeit small, does not find that the PADPRP pseudogene duplicated region located on chromosome 13 is a risk factor for lung cancer. 相似文献
5.
JM Langley JC LeBlanc EE Wang BJ Law NE MacDonald I Mitchell D Stephens J McDonald FD Boucher S Dobson 《Pediatrics》1997,100(6):943-946
OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality. 相似文献
6.
Louise Burke Douglas B Flieder Donald G Guinee Elizabeth Brambilla Andrew N Freedman William P Bennett Raymond T Jones Andrew Borkowski Neil A Caporaso Marian Fleming Victor Trastek Peter Pairolero Henry Tazelaar David Midthun James R Jett Lance A Liotta William D Travis Curtis C Harris 《Clinical cancer research》2005,11(1):232-241
PURPOSE: Many studies have highlighted the aberrant expression and prognostic significance of individual proteins in either the Rb (particularly cyclin D1, p16INK4A, and pRb) or the p53 (p53 and p21Waf1) pathways in non-small cell lung cancer. We hypothesize that cumulative abnormalities within each and between these pathways would have significant prognostic potential regarding survival. EXPERIMENTAL DESIGN: Our study population consisted of 106 consecutive surgically resected cases of predominantly early-stage non-small cell lung cancer from the National Cancer Institute-Mayo Clinic series, and assessment of proteins involved both immunohistochemical (cyclin D1, p21Waf1, pRb, p16INK4A, and p53) and mutational analysis (p53) in relationship to staging and survival. RESULTS: Cyclin D1 overexpression was noted in 48% of the tumors, p16INK4A negative in 53%, pRb negative in 17%, p53 immunopositive in 50%, p53 mutation frequency in 48%, and p21(Waf1) overexpression in 47%, none with prognostic significance. Cyclin D1 overexpression in pRb-negative tumors revealed a significantly worse prognosis with a mean survival of 2.3 years (P = 0.004). A simultaneous p53 mutation dramatically reduced the mean survival time to 0.9 years (P = 0.007). Cyclin D1 overexpression with either a p53 mutation or a p53 overexpression was also associated with a significantly poorer prognosis (P = 0.0033 and 0.0063, respectively). CONCLUSIONS: Some cumulative abnormalities in the Rb and p53 pathways (e.g., cyclin D1 overexpression and p53 mutations) significantly cooperate to predict a poor prognosis; however, the complexity of the cell cycle protein interaction in any given tumor warrants caution in interpreting survival results when specific protein abnormalities are taken in isolation. 相似文献
7.
Mutations in the tyrosine kinase domain of the epidermal growth factor receptor in non-small cell lung cancer. 总被引:4,自引:0,他引:4
Sei Hoon Yang Leah E Mechanic Ping Yang Maria Teresa Landi Elise D Bowman Jason Wampfler Daoud Meerzaman Kyeong Man Hong Felicia Mann Tatiana Dracheva Junya Fukuoka William Travis Neil E Caporaso Curtis C Harris Jin Jen 《Clinical cancer research》2005,11(6):2106-2110
We evaluated somatic genetic alterations in the kinase domain of the EGFR gene in the tumors of 219 non-small cell lung cancer patients of primarily Caucasian and African American origins. We identified 26 patients (12%) whose tumors had a mutation in the EGFR gene, and 11 (5%) patients carried novel genomic variations consistent with germ-line polymorphisms. All but one mutation were identified in Caucasian patients affected with adenocarcinoma. EGFR mutations were more frequent in women and in nonsmokers, but a significant portion of the affected patients were men (12 of 26) and current or past smokers accounted for half of the patients affected (13 of 26). Screening subjects with EGFR mutations may identify patients whose tumors could respond to targeted therapy using tyrosine kinase inhibitors. 相似文献
8.
Nataša Tasevska Amanda J. Cross Kevin W. Dodd Regina G. Ziegler Neil E. Caporaso Rashmi Sinha 《International journal of cancer. Journal international du cancer》2011,128(2):402-411
Recent epidemiological studies have suggested that red and processed meat may increase the risk of lung cancer. Possible underlying mechanisms include mutagens produced during high‐temperature cooking or preservation, or formed endogenously from heme iron in meat. We used data from 99,579 participants of both screened and nonscreened arms of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, aged 55–74 years, to investigate whether meat type, cooking method, doneness level, intake of specific meat mutagens 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline] (DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and benzo(a)pyrene (B(a)P)] and heme iron are associated with lung cancer. Participants' diet was assessed prospectively using a 124‐item food frequency questionnaire and an additional meat‐cooking module. Dietary data were used in conjunction with a database to estimate intake of MeIQx, DiMeIQx, PhIP, B(a)P and heme iron. After up to 8 years of follow‐up, 782 incident lung cancer cases were ascertained. Lung cancer risk was not associated with the consumption of either red (men: HRQ5 vs. Q1 = 1.11, 95% CI = 0.79–1.56, Ptrend = 0.42; women: HRQ5 vs. Q1 = 1.30, 95% CI = 0.87–1.95, Ptrend = 0.65) or processed meat (men: HRQ5 vs. Q1 = 1.12, 95% CI = 0.83–1.53, Ptrend = 0.22; women: HRQ5 vs. Q1 = 0.98, 95% CI = 0.68–1.41, Ptrend = 0.32) in multivariable models. High‐temperature cooking methods, level of meat doneness, meat mutagens and heme iron had no effect on lung cancer risk. In this population, we found no association between meat type, cooking method, doneness level or intake of specific meat mutagens or heme iron and lung cancer risk. 相似文献
9.
Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia
下载免费PDF全文
![点击此处可从《International journal of cancer. Journal international du cancer》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Fangyi Gu Han Zhang Paula L. Hyland Sonja Berndt Susan M. Gapstur William Wheeler the ELLIPSE consortium Christopher I. Amos Stephane Bezieau Heike Bickeb?ller Hermann Brenner Paul Brennan Jenny Chang‐Claude David V Conti Jennifer Anne Doherty Stephen B Gruber Tabitha A Harrison Richard B Hayes Michael Hoffmeister Richard S Houlston Rayjean J. Hung Mark A. Jenkins Peter Kraft Kate Lawrenson James McKay Sarah Markt Lorelei Mucci Catherine M. Phelan Conghui Qu Angela Risch Mary Anne Rossing H.‐Erich Wichmann Jianxin Shi Eva Schernhammer Kai Yu Maria Teresa Landi Neil E. Caporaso 《International journal of cancer. Journal international du cancer》2017,141(9):1794-1802
Circadian disruption has been linked to carcinogenesis in animal models, but the evidence in humans is inconclusive. Genetic variation in circadian rhythm genes provides a tool to investigate such associations. We examined associations of genetic variation in nine core circadian rhythm genes and six melatonin pathway genes with risk of colorectal, lung, ovarian and prostate cancers using data from the Genetic Associations and Mechanisms in Oncology (GAME‐ON) network. The major results for prostate cancer were replicated in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial, and for colorectal cancer in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). The total number of cancer cases and controls was 15,838/18,159 for colorectal, 14,818/14,227 for prostate, 12,537/17,285 for lung and 4,369/9,123 for ovary. For each cancer site, we conducted gene‐based and pathway‐based analyses by applying the summary‐based Adaptive Rank Truncated Product method (sARTP) on the summary association statistics for each SNP within the candidate gene regions. Aggregate genetic variation in circadian rhythm and melatonin pathways were significantly associated with the risk of prostate cancer in data combining GAME‐ON and PLCO, after Bonferroni correction (ppathway < 0.00625). The two most significant genes were NPAS2 (pgene = 0.0062) and AANAT (pgene = 0.00078); the latter being significant after Bonferroni correction. For colorectal cancer, we observed a suggestive association with the circadian rhythm pathway in GAME‐ON (ppathway = 0.021); this association was not confirmed in GECCO (ppathway = 0.76) or the combined data (ppathway = 0.17). No significant association was observed for ovarian and lung cancer. These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms. 相似文献
10.