全文获取类型
收费全文 | 619篇 |
免费 | 24篇 |
国内免费 | 34篇 |
专业分类
儿科学 | 23篇 |
妇产科学 | 6篇 |
基础医学 | 50篇 |
口腔科学 | 8篇 |
临床医学 | 51篇 |
内科学 | 66篇 |
皮肤病学 | 6篇 |
神经病学 | 7篇 |
特种医学 | 172篇 |
外科学 | 85篇 |
综合类 | 19篇 |
预防医学 | 38篇 |
眼科学 | 11篇 |
药学 | 20篇 |
中国医学 | 1篇 |
肿瘤学 | 114篇 |
出版年
2022年 | 2篇 |
2021年 | 1篇 |
2020年 | 1篇 |
2019年 | 4篇 |
2018年 | 6篇 |
2017年 | 3篇 |
2016年 | 8篇 |
2015年 | 14篇 |
2014年 | 13篇 |
2013年 | 11篇 |
2012年 | 11篇 |
2011年 | 20篇 |
2010年 | 24篇 |
2009年 | 38篇 |
2008年 | 28篇 |
2007年 | 37篇 |
2006年 | 42篇 |
2005年 | 37篇 |
2004年 | 25篇 |
2003年 | 17篇 |
2002年 | 18篇 |
2001年 | 28篇 |
2000年 | 16篇 |
1999年 | 23篇 |
1998年 | 28篇 |
1997年 | 36篇 |
1996年 | 23篇 |
1995年 | 14篇 |
1994年 | 9篇 |
1993年 | 13篇 |
1992年 | 8篇 |
1991年 | 9篇 |
1990年 | 9篇 |
1989年 | 20篇 |
1988年 | 21篇 |
1987年 | 11篇 |
1986年 | 11篇 |
1985年 | 12篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 2篇 |
1981年 | 5篇 |
1979年 | 2篇 |
1978年 | 1篇 |
1977年 | 3篇 |
1976年 | 1篇 |
1975年 | 3篇 |
排序方式: 共有677条查询结果,搜索用时 10 毫秒
1.
Molecular determinants of cetuximab efficacy. 总被引:17,自引:0,他引:17
Daniel Vallb?hmer Wu Zhang Michael Gordon Dong Yun Yang Jim Yun Oliver A Press Katrin E Rhodes Andy E Sherrod Syma Iqbal Kathleen D Danenberg Susan Groshen Heinz-Josef Lenz 《Journal of clinical oncology》2005,23(15):3536-3544
PURPOSE: To investigate whether mRNA expression levels of cyclin D1 (CCND1), cyclooxygenase 2 (Cox-2), epidermal growth factor receptor (EGFR), interleukin 8 (IL-8), and vascular endothelial growth factor (VEGF), all members of the EGFR signaling pathway, are associated with clinical outcome in patients with EGFR-expressing metastatic colorectal cancer (CRC) treated with cetuximab. PATIENTS AND METHODS: Thirty-nine patients with metastatic CRC, refractory to both irinotecan and oxaliplatin, were enrolled on IMCL-0144 and treated with single-agent cetuximab. The intratumoral mRNA levels of CCND1, Cox-2, EGFR, IL-8, and VEGF were assessed from paraffin-embedded tissue samples using laser-capture microdissection and quantitative real-time polymerase chain reaction. RESULTS: There were 21 women and 18 men with a median age of 64 years (range, 35 to 83 years). Higher gene expression levels of VEGF were associated with resistance to cetuximab (P = .038; Kruskal-Wallis test). The combination of low gene expression levels of Cox-2, EGFR, and IL-8 was significantly associated with overall survival (13.5 v 2.3 months; P = .028; log-rank test). Both findings were independent of skin toxicity that was itself significantly correlated to survival. Patients with a lower mRNA amount of EGFR had a longer overall survival compared with patients that had a higher mRNA amount (7.3 v 2.2 months; P = .09; log-rank test). Patients with lower expression of Cox-2 had a significantly higher rate of grade 2 to 3 skin reactions under cetuximab treatment. CONCLUSION: This pilot study suggests that gene expression levels of Cox-2, EGFR, IL-8, and VEGF in patients with metastatic CRC may be useful markers of clinical outcome in single-agent cetuximab treatment. 相似文献
2.
ZQ Yin MD SG Crewther PhD B Pirie BSc DP Crewther PhD 《Clinical & experimental ophthalmology》1997,25(4):107-109
Purpose: It was investigated whether alterations in neuronal structure and function occasioned by strabismic amblyopia also may be reflected in alterations in the expression on Y type neurons of a Cat-301 antibody sensitive antigen in the lateral geniculate nucleus (LGN) and cortex of our cat model of strabismic amblyopia. Methods/Results: The percentage of positively labelled cells was reduced in LGN laminae that received input from the deviated eye in strabismic amblyopic cats compared with normal cats. In the strabismic cortex, the density of immunopositive neurons was significantly reduced compared with normal, the effect being most pronounced in layer IV Conclusions: Despite previous physiological recordings indicating a decrease in X-cell associated acuity in strabismic amblyopia, the present findings imply that the changes in the early visual experience occasioned by strabismus also produce specific molecular changes in theY neuronal class. 相似文献
3.
Established nonexpanding hematomas can be successfully treated with minimal morbidity using standard liposucstion techniques at the bedside or in an outpatient setting under local anesthesia. The authors presents a series of eight patients and discuss current concepts of dealing with this common and distressing surgical complication. 相似文献
4.
SG Saarland 《MedR Medizinrecht》2004,22(5):279-282
Ohne Zusammenfassung 相似文献
5.
Viviane D Lima Patricia Kretz Anita Palepu Simon Bonner Thomas Kerr David Moore Mark Daniel Julio SG Montaner Robert S Hogg 《AIDS research and therapy》2006,3(1):14-9
Background
Although the impact of Aboriginal status on HIV incidence, HIV disease progression, and access to treatment has been investigated previously, little is known about the relationship between Aboriginal ethnicity and outcomes associated with highly active antiretroviral therapy (HAART). We undertook the present analysis to determine if Aboriginal and non-Aboriginal persons respond differently to HAART by measuring HIV plasma viral load response, CD4 cell response and time to all-cause mortality. 相似文献6.
A second locus (GLC3B) for primary congenital glaucoma (Buphthalmos) maps to the 1p36 region 总被引:10,自引:0,他引:10
Akarsu AN; Turacli ME; Aktan SG; Barsoum-Homsy M; Chevrette L; Sayli BS; Sarfarazi M 《Human molecular genetics》1996,5(8):1199-1203
Primary congenital glaucoma (gene symbol: GLC3) is an ocular disorder that
occurs for 0.01-0.04% of blind people. In the majority of familial cases
reported so far, this condition is inherited as an autosomal recessive
trait. We have recently used a group of 17 GLC3 families with a minimum of
two affected offspring and consanguinity in most of the parental generation
and mapped the first GLC3 locus (GLC3A) to the 2p21 region. Six families
did not show any linkage to the GLC3A locus and thus provided evidence for
genetic heterogeneity of this disorder. A total of eight families unlinked
to the 2p21 region were used to search for the chromosomal location of the
second GLC3 locus. Herein, we describe mapping of a new locus (designated
GLC3B) for primary congenital glaucoma to the short arm of chromosome 1
(1p36.2-36.1) that is situated centromeric to the neuroblastoma and
Charcot-Marie-Tooth type 2A (CMT2A) loci. A total of 17 DNA markers were
genotyped from this region of chromosome 1. Four families showed no
recombination with the two markers D1S2834 and D1S402 with a maximum lod
score of 4.510 and 4.157 respectively. Pairwise and multipoint linkage
analysis and inspection of the haplotypes revealed that the remaining four
families are not linked to this part of chromosome 1, thus providing
further evidence that at least one more locus for the autosomal recessive
form of GLC3 must exist in the genome. Based on the recombination events,
the overall linkage map of this region is: tel-D1S1192-D1S1635-D1S1193 -
(D1S1597/-D1S489/D1S228)- [GLC3B/D1S2834/D1S402] - (D1S1176/D1S507/D1S407)
- D1S2728-(MFAP2/D1S170) - D1S1368 - D1S436- D1S1592-cen.
相似文献
7.
Gang Wang Peter C. Black Peter J. Goebell Lingyun Ji Carlos Cordon-Cardo Bernd Schmitz-Dräger Debra Hawes Bogdan Czerniak Sarah Minner Guido Sauter Frederic Waldman Susan Groshen Richard J. Cote Colin P. Dinney 《Urologic oncology》2021,39(5):301.e17-301.e28
PurposeWe evaluated the prognostic value of 10 putative tumor markers by immunohistochemistry in a large multi-institutional cohort of patients with locally advanced urothelial cancer of the bladder (UCB) with the aim to validate their clinical value and to harmonize protocols for their evaluation.Materials and MethodsPrimary tumor specimens from 576 patients with pathologic (p)T3 UCB were collected from 24 institutions in North America and Europe. Three replicate 0.6-mm core diameter samples were collected for the construction of a tissue microarray (TMA). Immunohistochemistry (IHC) for 10 previously described tumor markers was performed and scored at 3 laboratories independently according to a standardized protocol. Associations between marker positivity and freedom from recurrence (FFR) or overall survival (OS) were analyzed separately for each individual laboratory using Cox regression analysis.ResultsThe overall agreement of the IHC scoring among laboratories was poor. Correlation among the 3 laboratories varied across the 10 markers. There was generally a lack of association between the individual markers and FFR or OS. The number of altered cell cycle regulators (p53, Rb, and p21) was associated with increased risk of cancer recurrence (P < 0.032). There was no clear pattern in the relationship between the percentage of markers altered in an 8-marker panel and FFR or OS.ConclusionsThis large international TMA of locally advanced (pT3) UCB suggests that altered expression of p53, Rb, and p21 is associated with worse outcome. However this study also highlights limitations in the reproducibility of IHC even in the most expert hands. 相似文献
8.
David Esrig John A. Freeman Donald A. Elmajian John P. Stein Su-Chiu Chen Susan Groshen Anne Simoneau Eila C. Skinner Gary Lieskovsky Stuart D. Boyd Richard J. Cote Donald G. Skinner 《The Journal of urology》1996,156(3):1071-1076
Purpose
We investigated the effect on survival of transitional cell carcinoma of the prostatic urethra, ducts and stroma, and determined the difference between prostatic stromal involvement occurring via direct extension through the bladder wall versus stromal invasion arising intraurethrally.Materials and Methods
Between August 1971 and December 1989, 489 men underwent radical cystoprostatectomy for transitional cell carcinoma, including 143 (29.2 percent) identified with prostate involvement by transitional cell carcinoma in the cystectomy specimen. Patients were separated into 2 groups: 1–19 in whom the primary bladder tumor extended full thickness through the bladder wall to invade the prostate (classified as P4a) and 2–124 in whom prostate involvement arose from within the prostatic urethra.Results
Five-year recurrence-free and overall survival rates were 25 and 21 percent, respectively, in group 1 versus 64 and 55 percent, respectively, in group 2. In the 124 patients in group 2 survival rates were similar for those with prostatic urethral tumors or carcinoma in situ and ductal tumors (no stromal invasion). Five-year overall survival rates without and with stromal invasion were 71 and 36 percent, respectively (p less than 0.0001). Transitional cell carcinoma of the prostatic urethra or ducts does not alter survival predicted by primary bladder stage alone. Prostatic stromal invasion arising intraurethrally significantly decreases survival, which varies based on primary bladder stage (64.6 percent in stage P1, 30.8 percent in stages P2/P3a and 13.6 percent in stage P3b, p = 0.0001). P1 bladder tumors with prostatic stromal invasion arising intraurethrally had a significantly higher survival rate than P4a tumors (64.6 versus 21 percent, p = 0.0001). P3b bladder tumors with stromal invasion had a survival rate similar to that of P4a tumors (p = 0.78).Conclusions
Prostatic urethral or ductal transitional cell carcinoma does not alter survival determined by primary bladder stage alone and it should not be classified as P4a. Prostatic stromal involvement arising intraurethrally significantly decreases survival predicted by primary bladder stage alone. P1 bladder tumors with prostatic stromal invasion arising intraurethrally have a significantly higher survival rate than P4a tumors and they should be separately classified as P1str. Muscle invasive (P2/P3a) bladder tumors with stromal invasion have a higher survival rate than P4a tumors (no statistical significance) and they should be designated separately (that is P2str). P3b bladder tumors with prostatic stromal invasion arising intraurethrally are indistinguishable from P4a tumors. 相似文献9.
Xiaowei Yang Susan Groshen Silvia C Formenti Nancy E Davidson Michael F Press 《Clinical cancer research》2003,9(1):201-206
PURPOSE: Evaluate p7 expression in human breast cancer and determine whether chemotherapy and radiation therapy effect a change in p7 expression. EXPERIMENTAL DESIGN: Using a p7-specific monoclonal antibody with immunohistochemistry and Western immunoblot analyses to assess p7 expression in archival, frozen breast cancer specimens both before and after therapy. RESULTS: A novel 7 kDa protein (p7), originally identified in multidrug-resistant ovarian and breast cancer cell lines, was found to be expressed in 21 of 64 (32%) primary, unselected human breast cancer specimens by immunohistochemistry with the use of a p7-specific monoclonal antibody, 1D7. P7 was observed in malignant cells but not in other types of cells in the breast tissue. Western blot analysis confirmed the 7 kDa polypeptide in p7-positive breast carcinomas identified by immunohistochemistry. P7 expression was significantly associated with breast cancers having distant metastasis and/or local recurrence (P = 0.027, Fisher's exact test). In addition, p7 expression was significantly increased in post-treatment breast cancer biopsy specimens compared with pretreatment breast cancer biopsy specimens in patients with locally advanced breast cancer after 5-fluorouracil chemotherapy and radiation therapy [2 of 15 (13%) pretreatment breast cancers compared with 8 of 15 (53%) post-treatment breast cancers; P = 0.016, McNemar's test]. CONCLUSIONS: These findings demonstrate that expression of p7 is associated with malignant tumor cells in primary breast cancers, especially those showing recurrent or metastatic disease. Its specific association with the malignant phenotype suggests it may have potential for novel target-based therapies. The markedly increased expression in patients with locally advanced disease after neoadjuvant therapy suggests a role for p7 in treatment outcome. 相似文献
10.