全文获取类型
收费全文 | 831篇 |
免费 | 67篇 |
专业分类
耳鼻咽喉 | 13篇 |
儿科学 | 11篇 |
妇产科学 | 70篇 |
基础医学 | 89篇 |
口腔科学 | 7篇 |
临床医学 | 40篇 |
内科学 | 118篇 |
皮肤病学 | 4篇 |
神经病学 | 89篇 |
特种医学 | 15篇 |
外科学 | 47篇 |
综合类 | 1篇 |
预防医学 | 52篇 |
眼科学 | 3篇 |
药学 | 135篇 |
肿瘤学 | 204篇 |
出版年
2022年 | 3篇 |
2021年 | 7篇 |
2020年 | 14篇 |
2019年 | 10篇 |
2018年 | 15篇 |
2017年 | 11篇 |
2016年 | 12篇 |
2015年 | 15篇 |
2014年 | 20篇 |
2013年 | 16篇 |
2012年 | 33篇 |
2011年 | 39篇 |
2010年 | 19篇 |
2009年 | 15篇 |
2008年 | 25篇 |
2007年 | 38篇 |
2006年 | 32篇 |
2005年 | 29篇 |
2004年 | 35篇 |
2003年 | 36篇 |
2002年 | 31篇 |
2001年 | 48篇 |
2000年 | 34篇 |
1999年 | 30篇 |
1998年 | 7篇 |
1997年 | 9篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 10篇 |
1993年 | 5篇 |
1992年 | 30篇 |
1991年 | 28篇 |
1990年 | 35篇 |
1989年 | 33篇 |
1988年 | 19篇 |
1987年 | 19篇 |
1986年 | 17篇 |
1985年 | 15篇 |
1984年 | 18篇 |
1983年 | 9篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 9篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1974年 | 7篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1971年 | 4篇 |
1966年 | 3篇 |
排序方式: 共有898条查询结果,搜索用时 15 毫秒
91.
Pokala N Delaney CP Kiran RP Bast J Angermeier K Fazio VW 《International journal of colorectal disease》2007,22(6):683-687
Objectives Prophylactic insertion of ureteric stents aids intra-operative identification of ureters and may allow easier visualization
of any direct ureteric injury. Traditionally, ureteric catheters are inserted sequentially, before starting the abdominal
part of the operation. This study determines the safety and efficacy of simultaneous intra-operative ureteric catheter insertion
during complicated and re-operative colorectal surgery.
Materials and methods After institutional review board (IRB) approval, 24 patients were randomized into two groups, sequential (SEQ) and simultaneous
(SIM) depending upon the timing of stent placement relative to abdominal incision. Time taken from induction to abdominal
incision (AIT), induction to peritoneal entry (PET), catheter insertion time (CIT), and urinary tract infection rates were
recorded. Degree of difficulty for stent insertion was graded on a scale of 1–10.
Result Demographics were similar between groups. Mean AIT (22 ± 4 vs 41 ± 7; p = 0.0001) and mean PET (26 ± 4.2 vs 44 ± 7.6; p = 0.0001) were shorter in the SIM group. There was no significant difference in mean CIT in SIM and SEQ groups (17.9 ± 4.9
vs 17.6 ± 5.9 min, p = 0.8). The stents were unsuccessful bilaterally in one patient in the SEQ group and unilaterally in two other patients,
one in each group. The median difficulty score for catheter insertion was 3 (1–10) and 2 (1–10), (p = 0.12), respectively, in SIM and SEQ groups. There were no ureteric injuries in either group. One patient in SIM developed
a urinary tract infection.
Conclusion Simultaneous ureteric catheter insertion during abdominal procedures reduces operating times without a significant increase
in morbidity. Furthermore, this permits a policy of selective stent insertion as required by the intra-abdominal findings
after laparotomy. 相似文献
92.
Kaiserová H Simunek T Sterba M den Hartog GJ Schröterová L Popelová O Gersl V Kvasnicková E Bast A 《Cardiovascular toxicology》2007,7(2):145-150
The use of anthracycline anticancer drugs is limited by a cumulative, dose-dependent cardiac toxicity. Iron chelation has
long been considered as a promising strategy to limit this unfavorable side effect, either by restoring the disturbed cellular
iron homeostasis or by removing redox-active iron, which may promote anthracycline-induced oxidative stress. Aroylhydrazone
lipophilic iron chelators have shown promising results in the rabbit model of daunorubicin-induced cardiomyopathy as well
as in cellular models. The lack of interference with the antiproliferative effects of the anthracyclines also favors their
use in clinical settings. The dose, however, should be carefully titrated to prevent iron depletion, which apparently also
applies for other strong iron chelators. We have shown that a mere ability of a compound to chelate iron is not the sole determinant
of a good cardioprotector and the protective potential does not directly correlate with the ability of the chelators to prevent
hydroxyl radical formation. These findings, however, do not weaken the role of iron in doxorubicin cardiotoxicity as such,
they rather appeal for further investigations into the molecular mechanisms how anthracyclines interact with iron and how
iron chelation may interfere with these processes. 相似文献
93.
Sequist LV Heist RS Shaw AT Fidias P Rosovsky R Temel JS Lennes IT Digumarthy S Waltman BA Bast E Tammireddy S Morrissey L Muzikansky A Goldberg SB Gainor J Channick CL Wain JC Gaissert H Donahue DM Muniappan A Wright C Willers H Mathisen DJ Choi NC Baselga J Lynch TJ Ellisen LW Mino-Kenudson M Lanuti M Borger DR Iafrate AJ Engelman JA Dias-Santagata D 《Annals of oncology》2011,22(12):2616-2624
BackgroundPersonalizing non-small-cell lung cancer (NSCLC) therapy toward oncogene addicted pathway inhibition is effective. Hence, the ability to determine a more comprehensive genotype for each case is becoming essential to optimal cancer care.MethodsWe developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes. SNaPshot and FISH for ALK translocations were integrated into routine practice as Clinical Laboratory Improvement Amendments-certified tests. Here, we present analyses of the first 589 patients referred for genotyping.ResultsPathologic prescreening identified 552 (95%) tumors with sufficient tissue for SNaPshot; 51% had ≥1 mutation identified, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%) and translocations involving ALK (5%). Unanticipated mutations were observed at lower frequencies in IDH and β-catenin. We observed several associations between genotypes and clinical characteristics, including increased PIK3CA mutations in squamous cell cancers. Genotyping distinguished multiple primary cancers from metastatic disease and steered 78 (22%) of the 353 patients with advanced disease toward a genotype-directed targeted therapy.ConclusionsBroad genotyping can be efficiently incorporated into an NSCLC clinic and has great utility in influencing treatment decisions and directing patients toward relevant clinical trials. As more targeted therapies are developed, such multiplexed molecular testing will become a standard part of practice. 相似文献
94.
Vose JM Weisenburger DD Loberiza FR Arevalo A Bast M Armitage J Bierman PJ Bociek RG Armitage JO 《British journal of haematology》2010,151(4):354-358
The outcomes for 162 patients with diffuse large B-cell lymphoma treated with a CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone)-like regimen who obtained a complete remission and who subsequently relapsed after ≥5 years of remission (late relapse, N=30), or <5 years of remission (early relapse, N=132), were compared. The late relapsing patients had better prognostic characteristics at diagnosis, such as stage I/II disease (73% vs. 49%, P=0·04), a normal lactic dehydrogenase (77% vs. 48%, P=0·01), and a Karnofsky performance score of ≥80 (100% vs. 86%, P=0·01). The 3-year survival after relapse was better in late relapsing patients (48% vs. 25%, P=0·03), but the survival at 5 years (32% vs. 20%) and 10 years (13% vs. 14%) after relapse was not different. A multivariate analysis of factors predicting survival after relapse found age (P<0·0001) and presence of B-symptoms (P=0·03) to predict survival, but not early versus late relapse. A small percentage of the late relapsing patients can have a prolonged second remission. However, the overall survival from the time of relapse was not different between early and late relapsing patients with most succumbing to lymphoma. 相似文献
95.
96.
Correlation between CpG methylation profiles and hormone receptor status in breast cancers
下载免费PDF全文
![点击此处可从《Breast cancer research : BCR》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Feng W Shen L Wen S Rosen DG Jelinek J Hu X Huan S Huang M Liu J Sahin AA Hunt KK Bast RC Shen Y Issa JP Yu Y 《Breast cancer research : BCR》2007,9(4):R57-13
Introduction
Aberrant DNA methylation has been found frequently in human breast cancers, associated with the loss of expression of a number of regulatory genes for growth and correlated to clinical outcomes. The present study was undertaken to determine whether methylation of a set of growth-suppressor genes would correlate to the expression of estrogen receptors (ERs) and progesterone receptors (PRs).Methods
We used a pyrosequencing methylation analysis to study the methylation of 12 known growth-suppressor genes in 90 pairs of malignant/normal breast tissues. We also examined the expression of ERs and PRs in those specimens by immunohistochemistry. Mutations of p53 in tumor cells were detected by direct sequencing.Results
Twelve tumor-suppressor genes: ARHI, RASSF1A, HIN-1, RARβ2, hMLH1, 14-3-3 σ, RIZ1, p16, E-cadherin, RIL, CDH13, and NKD2 were selected for this methylation study. Five of them (RIL, HIN-1, RASSF1A, CDH13, and RARβ2) were frequently methylated in breast cancers (57%, 49%, 58%, 44%, and 17%, respectively) but not the normal breast (0–4%). Two panels of methylation profiles were defined. The methylation of the HIN-1/RASSFIA panel strongly correlated to the expression of ERs, PRs, and hormone receptors (HRs; which were defined as 'positive' if ERs and/or PRs were positive; p < 0.001). Conversely, the methylation of the RIL/CDH13 panel strongly correlated to negative ER, PR, and HR expression (p = 0.001, 0.025, and 0.001, respectively). The subset of triple-negative breast cancers (in other words, those with negative ER, PR, and HER-2/neu status) was positively associated with the methylation of the RIL/CDH13 panel and negatively associated with the HIN-1/RASSF1A panel. Mutations of p53 were found in nine breast tumors (11%), seven of which lacked methylation in both panels.Conclusion
We have defined two panels (HIN-1/RASSFIA, and RIL/CDH13) of methylation profiles, which correlated, either positively or negatively, to HR status. 相似文献97.
Philippi H Wohlrab G Bettendorf U Borusiak P Kluger G Strobl K Bast T 《Epilepsia》2008,49(11):1859-1864
Purpose: A retrospective study for a classification of prehypsarrhythmic elecroencephalographies (EEGs) was carried out to enable an early treatment option for West syndrome. Methods: Out of 39 infants with symptomatic West syndrome, 18 infants (age 3–14 months) with 61 serial non‐REM sleep EEG records of the prehypsarrhythmic phase were identified. The prehypsarrhythmic phase encompassed 2 to 13 months (mean 4.5 months) after an initial insult. A classification system of three EEG types corresponding to the clinical states prior to West syndrome occurrence was developed. In addition, follow‐up of all patients presenting with type 2 EEGs (n = 22) was evaluated. Results: Three clinical states and corresponding EEG types were classified. Clinical state 1 (weeks to months, silent phase) presented with (multi‐)focal epileptic discharges <50% of the non‐REM EEG recording time (type 1 EEG). Clinical state 2 (several weeks, beginning mental deterioration) was accompanied by type 2 EEG with bihemispheric epileptic discharges >50% of the non‐REM EEG recording time within abnormal background activity (imminent hypsarrhythmia). Clinical state 3 (mental deterioration) was characterized by hypsarryhthmia. Interrater reliability of seven blinded raters was good (median weighted κ 0.67). Out of 22 patients presenting with type 2 EEGs, two were lost for follow‐up, and 16 developed West syndrome, whereas four were treated early with anti‐epileptic drugs and remained stable. Conclusions: Infants with West syndrome could be reliably identified several weeks before the occurrence of hypsarrhythmia by a typical EEG pattern (type 2), thereby opening the way for early intervention studies. 相似文献
98.
Fauser S Bast T Altenmüller DM Schulte-Mönting J Strobl K Steinhoff BJ Zentner J Schulze-Bonhage A 《Journal of neurology, neurosurgery, and psychiatry》2008,79(1):103-105
A total of 120 patients with histologically proven focal cortical dysplasias (FCD) were retrospectively analysed for prognostic factors for successful epilepsy surgery. Multivariate data analyses showed that older age at epilepsy surgery, occurrence of secondarily generalised seizures and a multilobar extent of the dysplasia were significant negative predictors. In univariate analyses, longer duration of epilepsy, need for intracranial EEG recordings and incomplete resection of the FCD were factors which significantly reduced the chance of becoming seizure free. Histological subtype of the FCD and age at epilepsy onset had no significant predictive value. These findings strongly suggest early consideration of epilepsy surgery in FCD patients. 相似文献
99.
100.
Knockdown of p53 combined with expression of the catalytic subunit of telomerase is sufficient to immortalize primary human ovarian surface epithelial cells 总被引:11,自引:0,他引:11
Yang G Rosen DG Mercado-Uribe I Colacino JA Mills GB Bast RC Zhou C Liu J 《Carcinogenesis》2007,28(1):174-182
Ovarian cancer is developed from a single layer of thin epithelial cells covering the surface of ovary, named human ovarian surface epithelial cells. Like all primary human cells, human ovarian surface epithelial cells have a finite life span and will go into senescence and eventually die when cultured in vitro. Immortalized human ovarian surface epithelial cells will provide an important model system with which to study ovarian cancer initiation and progression. Here, we show that silencing p53 expression with retrovirus-mediated small interfering RNA can delay the senescence and extend cell passage number, but is not sufficient to immortalize normal ovarian surface epithelial cells. Introduction of the catalytic subunit of telomerase is similarly insufficient to achieve immortalization. However, concurrent disruption of p53 expression with small interfering RNA retroviral constructs and ectopic expression of the catalytic subunit of telomerase was sufficient to induce cellular immortalization in 3 of 3 human ovarian surface epithelial cell cultures tested. The immortalization is associated with increased telomerase activity and telomere length, and attenuated response of cell-cycle regulatory proteins to irradiation. The resultant immortal cells continued to express the same specific cytokeratins 8 and 18 as parental cells did, indicating that the epithelial characters are still maintained in the immortal cells. In addition, the immortalized cells are non-tumorigenic and nearly diploid, which is in constrast with one immortalized by SV40 T/t antigens and hTERT. As both p53 pathway dysfunction and activation of telomerase are commonly present in human ovarian cancer, these immortal cells provide an authetic cell model system for the study of the human ovarian cancer initiation, progression, differentiation and chemoprevention. 相似文献