全文获取类型
收费全文 | 3096篇 |
免费 | 213篇 |
国内免费 | 21篇 |
学科分类
医药卫生 | 3330篇 |
出版年
2023年 | 13篇 |
2022年 | 11篇 |
2021年 | 55篇 |
2020年 | 41篇 |
2019年 | 68篇 |
2018年 | 75篇 |
2017年 | 66篇 |
2016年 | 70篇 |
2015年 | 99篇 |
2014年 | 120篇 |
2013年 | 164篇 |
2012年 | 258篇 |
2011年 | 255篇 |
2010年 | 142篇 |
2009年 | 138篇 |
2008年 | 233篇 |
2007年 | 221篇 |
2006年 | 193篇 |
2005年 | 212篇 |
2004年 | 181篇 |
2003年 | 164篇 |
2002年 | 177篇 |
2001年 | 22篇 |
2000年 | 14篇 |
1999年 | 13篇 |
1998年 | 32篇 |
1997年 | 13篇 |
1996年 | 8篇 |
1995年 | 20篇 |
1994年 | 21篇 |
1993年 | 14篇 |
1992年 | 14篇 |
1991年 | 7篇 |
1990年 | 7篇 |
1989年 | 8篇 |
1988年 | 10篇 |
1987年 | 9篇 |
1986年 | 9篇 |
1985年 | 10篇 |
1984年 | 10篇 |
1983年 | 8篇 |
1982年 | 16篇 |
1981年 | 10篇 |
1980年 | 14篇 |
1979年 | 9篇 |
1978年 | 7篇 |
1976年 | 6篇 |
1974年 | 6篇 |
1962年 | 5篇 |
1961年 | 5篇 |
排序方式: 共有3330条查询结果,搜索用时 31 毫秒
1.
Emilie M.J. van Brummelen Sanne Huijberts Carla van Herpen Ingrid Desar Frans Opdam Robin van Geel Serena Marchetti Neeltje Steeghs Kim Monkhorst Bas Thijssen Hilde Rosing Alwin Huitema Jos Beijnen Rene Bernards Jan Schellens 《The oncologist》2021,26(4):290-e545
Lessons Learned
- Afatinib and selumetinib can be combined in continuous and intermittent dosing schedules, albeit at lower doses than approved for monotherapy.
- Maximum tolerated dose for continuous and intermittent schedules is afatinib 20 mg once daily and selumetinib 25 mg b.i.d.
- Because the anticancer activity was limited, further development of this combination is not recommended until better biomarkers for response and resistance are defined.
2.
Willy Baccaglini Felipe A. Glina Cristiano Linck Pazeto Luis G. Medina Fernando Korkes Wanderley M. Bernardo Rene Sotelo Sidney Glina Giancarlo Marra Marco Moschini Xavier Cathelineau Rafael Sanchez-Salas 《Clinical genitourinary cancer》2021,19(1):3-11.e1
This meta-analysis focuses on the accuracy of upgrading to clinically significant prostate cancer (PCa) by multiparametric magnetic resonance imaging-targeted biopsy (MRI-TB) versus systematic biopsy (SB). We searched the Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Literatura Latino Americana em Ciências da Saúde databases through January 2020 for comparative, retrospective/prospective, paired-cohort, and randomized clinical trials with paired comparisons. The population consisted of patients with low-risk PCa in active surveillance with at least 1 index lesion on imaging. We evaluated the quality of evidence by using the Quality Assessment of Diagnostic Accuracy Studies-2 score. Group comparisons considered the differences between the area under the curve summary receiver operating characteristic curve in a 2-tailed method. We also compared the positive predictive value of the best single method (MRI-TB or SB) and the referral study test (combined biopsy, a combination of MRI-TB and SB). The meta-analysis included 6 studies enrolling 741 patients. The pooled sensitivity for the 2 groups was 0.79 (95% confidence interval, 0.74-0.83; I2 = 75%) and 0.67 (95% confidence interval, 0.63-0.74; I2 = 55.4%), respectively. The area under the curve for the MRI-TB and SB groups were 0.99 and 0.92 (P < .001), respectively. The positive predictive value for the MRI-TB and combined biopsy groups were similar. The accumulated evidence suggests better results for MRI-TB compared with SB. Therefore, use of MRI-TB alone may be preferable in patients in active surveillance harboring low-risk PCa. 相似文献
3.
Shafqat R. Chaudhry Ilana S. Lendvai Sajjad Muhammad Philipp Westhofen Johannes Kruppenbacher Lukas Scheef Henning Boecker Dirk Scheele Rene Hurlemann Thomas M. Kinfe 《Brain stimulation》2019,12(3):643-651
Objective
To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.Methods
This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls.Results
No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p?<?0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p?>?0.05]. No severe device-/stimulation-related adverse events occurred.Conclusion
2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]. 相似文献4.
5.
Ahmed Elhassanny Rene Escobedo Daniel Ladin Colin Burns Rukiyah Van Dross 《Oncotarget》2020,11(52):4788
Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15dPMJ2). As such, the current study investigates whether 15dPMJ2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ2-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ2-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ2 and the ER stress pathway. These results demonstrate that 15dPMJ2 is a tumor-selective inducer of DAMP signaling in melanoma. 相似文献
6.
7.
Rene S. Hendriksen Pimlapas Leekitcharoenphon Matthew Mikoleit Jacob Dyring Jensen Rolf Sommer Kaas Louise Roer Heena B. Joshi Srirat Pornruangmong Chaiwat Pulsrikarn Gladys D. Gonzalez-Aviles E. Ascelijn Reuland Nashwan Al Naiemi Astrid Louise Wester Frank M. Aarestrup Henrik Hasman 《Journal of clinical microbiology》2015,53(2):677-680
One unreported case of extended-spectrum-beta-lactamase (ESBL)-producing Salmonella enterica serovar Typhi was identified, whole-genome sequence typed, among other analyses, and compared to other available genomes of S. Typhi. The reported strain was similar to a previously published strain harboring blaSHV-12 from the Philippines and likely part of an undetected outbreak, the first of ESBL-producing S. Typhi. 相似文献
8.
9.
Alma Ghirelli MD Nirubol Tosakulwong BS Stephen D. Weigand MS Heather M. Clark PhD Farwa Ali MD Hugo Botha MD Joseph R. Duffy PhD Rene L. Utianski PhD Marina Buciuc MD Melissa E. Murray PhD Sydney A. Labuzan MS Anthony J. Spychalla BS Nha Trang Thu Pham BS Christopher G. Schwarz PhD Matthew L. Senjem MS Mary M. Machulda PhD Matthew Baker BS Rosa Rademakers PhD Massimo Filippi MD Clifford R. Jack Jr MD Val J. Lowe MD Joseph E. Parisi MD Dennis W. Dickson MD Keith A. Josephs MD MST MSc Jennifer L. Whitwell PhD 《Annals of neurology》2020,88(5):1009-1022
10.
Anthony W. Tolcher Razelle Kurzrock Vincente Valero Rene Gonzalez Rebecca S. Heist Antoinette R. Tan Julie Means-Powell Theresa L. Werner Carlos Becerra Chenxi Wang Cathrine Leonowens Shanker Kalyana-Sundaram Joseph F. Kleha Jennifer Gauvin Anthony M. DAmelio Catherine Ellis Nageatte Ibrahim Li Yan 《Cancer chemotherapy and pharmacology》2020,85(4):673-683
This study aimed to determine the safety, tolerability, and recommended phase II doses of trametinib plus uprosertib (GSK2141795) in patients with solid tumors likely to be sensitive to MEK and/or AKT inhibition. This was a phase I, open-label, dose-escalation, and dose-expansion study in patients with triple-negative breast cancer or BRAF-wild type advanced melanoma. The primary outcome of the expansion study was investigator-assessed response. Among 126 enrolled patients, 63 received continuous oral daily dosing of trametinib and uprosertib, 29 received various alternative dosing schedules, and 34 were enrolled into expansion cohorts. Doses tested in the expansion cohort were trametinib 1.5 mg once daily (QD) + uprosertib 50 mg QD. Adverse events (AEs) were consistent with those reported in monotherapy studies but occurred at lower doses and with greater severity. Diarrhea was the most common dose-limiting toxicity; diarrhea and rash were particularly difficult to tolerate. Overall, 59% and 6% of patients reported AEs with a maximum severity of grade 3 and 4, respectively. Poor tolerability prevented adequate delivery of uprosertib with trametinib at a concentration predicted to have clinical activity. The study was terminated early based on futility in the continuous-dosing expansion cohorts and a lack of pharmacological or therapeutic advantage with intermittent dosing. The objective response rate was < 5% (1 complete response, 5 partial responses). Continuous and intermittent dosing of trametinib in combination with uprosertib was not tolerated, and minimal clinical activity was observed in all schedules tested. 相似文献