全文获取类型
收费全文 | 1557篇 |
免费 | 94篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 69篇 |
妇产科学 | 15篇 |
基础医学 | 293篇 |
口腔科学 | 27篇 |
临床医学 | 137篇 |
内科学 | 285篇 |
皮肤病学 | 87篇 |
神经病学 | 159篇 |
特种医学 | 55篇 |
外科学 | 191篇 |
综合类 | 7篇 |
预防医学 | 84篇 |
眼科学 | 16篇 |
药学 | 65篇 |
肿瘤学 | 157篇 |
出版年
2023年 | 10篇 |
2022年 | 22篇 |
2021年 | 41篇 |
2020年 | 22篇 |
2019年 | 26篇 |
2018年 | 40篇 |
2017年 | 26篇 |
2016年 | 31篇 |
2015年 | 39篇 |
2014年 | 45篇 |
2013年 | 65篇 |
2012年 | 113篇 |
2011年 | 119篇 |
2010年 | 85篇 |
2009年 | 85篇 |
2008年 | 131篇 |
2007年 | 105篇 |
2006年 | 126篇 |
2005年 | 81篇 |
2004年 | 83篇 |
2003年 | 85篇 |
2002年 | 78篇 |
2001年 | 22篇 |
2000年 | 13篇 |
1999年 | 21篇 |
1998年 | 18篇 |
1997年 | 8篇 |
1996年 | 9篇 |
1995年 | 6篇 |
1994年 | 12篇 |
1993年 | 12篇 |
1992年 | 8篇 |
1991年 | 6篇 |
1990年 | 7篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 3篇 |
1985年 | 3篇 |
1982年 | 5篇 |
1981年 | 6篇 |
1980年 | 8篇 |
1979年 | 4篇 |
1978年 | 6篇 |
1977年 | 4篇 |
1976年 | 3篇 |
1975年 | 2篇 |
1974年 | 4篇 |
1973年 | 3篇 |
1972年 | 5篇 |
1966年 | 2篇 |
排序方式: 共有1673条查询结果,搜索用时 15 毫秒
21.
Elevated expression level of survivin protein in soft-tissue sarcomas is a strong independent predictor of survival. 总被引:17,自引:0,他引:17
Matthias Kappler Matthias Kotzsch Frank Bartel Susanne Füssel Christine Lautenschl?ger Uta Schmidt Peter Würl Matthias Bache Hannelore Schmidt Helge Taubert Axel Meye 《Clinical cancer research》2003,9(3):1098-1104
PURPOSE: Survivin is a member of the inhibitor-of-apoptosis gene family and is known to be overexpressed in a number of tumor types. The aim of this study was to evaluate the prognostic value of survivin protein expression in tumor tissue extracts in a group of well-characterized soft-tissue sarcoma (STS) patients. EXPERIMENTAL DESIGN: In this investigation, malignant tissue samples from 63 STS patients as well as from a panel of tumor cell lines were investigated, with nonmalignant tissues serving as controls. The survivin protein level was quantified by a novel ELISA and by Western blot analysis. Results obtained by both methods were compared with clinicopathological parameters regarding tumor grade and tumor entity, and they were then correlated to survival in a multivariate Cox regression model. RESULTS: High survivin levels were detected by ELISA and Western blot analysis in tumor tissue extracts and in lysates of tumor cell lines. None or only weak expression of survivin protein was found in nonmalignant cells and tissues. When comparing survivin values obtained by ELISA or Western blot, we found a significant correlation between both methods (P = 0.013, Pearson test). Our findings revealed that, in multivariate Cox regression analyses, survivin levels measured by ELISA and Western blot were significantly associated with tumor-related death in STS patients (P = 0.001, RR = 19.8, and P = 0.004, RR = 5.1, respectively). However, in a direct comparison of both survivin protein detection assays, we found a higher sensitivity and a stronger correlation to prognosis in survivin ELISA as compared with the Western blot assays. Furthermore, a higher tumor grade and more aggressive STS entity showed an elevated survivin protein expression level. CONCLUSION: Altogether, an elevated survivin content in tumor tissue extracts has a significant and independent negative predictive value on the survival-rate of STS patients. This finding corresponds well to data obtained for the mRNA level of survivin, as shown previously (M. Kappler et al., Int. J. Cancer, 95: 360-363, 2001). 相似文献
22.
Steinar Aamdal Uta Bruntsch Jean Kerger Jaap Verweij Wim Bokkel Huinink Jantien Wanders Ram Rastogi Hillary R. Franklin Stan B. Kaye 《Cancer chemotherapy and pharmacology》1997,40(5):439-443
The antitumor activity of zeniplatin, a third-generation, water-soluble platinum compound that has shown broad preclinical
antitumor activity and no significant nephrotoxicity in phase I trials, was tested in patients with advanced malignant melanoma
and advanced renal cancer. Patients who had not previously been treated, except with local limb perfusion and immunotherapy,
were given zeniplatin as bolus injections at 125 mg/m2 every 3 weeks. The main hematological toxicity was leukopenia (7/30 patients, WHO grade ≥ 3) and the main nonhematological
toxicity was nausea and vomiting (21/30 patients, WHO grade ≥ 2). Serious nephrotoxicity was observed early in the renal cancer
study and, later, also in the melanoma study. Hyperhydration did not prevent the nephrotoxicity, and the studies were stopped
after 6 renal cancer patients and 24 malignant melanoma patients had been included. Zeniplatin gave objective responses in
3 of the 21 evaluable malignant melanoma patients [2 complete responses (CRs) in patients with lymph-node metastases lasted
5 and 14 months, respectively; 1 partial response (PR) in a patient with lymph-node and liver metastases lasted 6 months].
In the renal cancer study, only four patients were evaluable for response and none responded. The results show that zeniplatin
has some activity (14%) in patients with advanced malignant melanoma, but no conclusion can be drawn regarding the activity
of zeniplatin in renal cancer as the number of patients was too low. The main toxicities were leukopenia and nausea and vomiting.
Unexpected and serious nephrotoxicity was observed, and for this reason the studies were terminated before the planned number
of patients had been included. A possible explanation for the nephrotoxicity may be drug interactions, but no firm conclusion
can yet be drawn.
Received: 16 March 1996 / Accepted: 25 March 1997 相似文献
23.
Sonja Loges Gerhard Heil Melanie Bruweleit Volker Schoder Martin Butzal Uta Fischer Ursula M Gehling Gunter Schuch Dieter K Hossfeld Walter Fiedler 《Journal of clinical oncology》2005,23(6):1109-1117
PURPOSE: Bone marrow neoangiogenesis plays an important pathogenetic and possible prognostic role in acute myeloid leukemia (AML). Members of the vascular endothelial growth factor (VEGF) and angiopoietin family represent the most specific inducers of angiogenesis secreted by AML blasts. We therefore correlated expression of angiogenic factors with clinical variables. PATIENTS AND METHODS: We investigated the expression of VEGF-A, VEGF-C, angiopoietin-1 (Ang1), angiopoietin-2 (Ang2), and the receptor Tie2 by quantitative polymerase chain reaction in a cohort of 90 patients younger than 61 years with de novo AML entered into the German AML Süddeutsche H?moblastose Gruppe Hannover 95 trial. Uni- and multivariate analyses were performed using clinical and gene expression variables. RESULTS: Univariate analysis of overall survival indicated the following variables as prognostic factors: good response on a day-15 bone marrow examination after initiation of induction chemotherapy, karyotype, and high Ang2 expression. In multivariate analysis, only bad response and log Ang2 expression remained of statistical significance, with a hazard ratio of 3.51 (95% CI, 1.91 to 6.47) and 0.75 (95% CI, 0.61 to 0.91), respectively. Subgroup analysis suggested that the prognostic impact of Ang2 expression was especially evident in cohorts with low VEGF-C and Ang1 mRNA levels. CONCLUSION: These results show that expression of Ang2 represents an independent prognostic factor in AML. Additional research into interactions of angiogenic cytokines in the pathogenesis of bone marrow angiogenesis in AML is warranted. 相似文献
24.
Incidents with toxic benthic cyanobacteria blooms have been increasing recently. In 2019, several dogs were poisoned in the river Lech (Germany) by the benthic anatoxin-a-producing genus Tychonema. To characterize spatial and temporal distribution of potentially toxic Tychonema in this river, a systematic monitoring was carried out in 2020, focusing on the occurrence of the genus, its toxin production and habitat requirements. Tychonema and cyanobacterial community composition in benthic mats and pelagic samples were identified using a combined approach of microscopy and DNA sequencing of the 16S rRNA gene. In addition, anatoxin-a concentrations of selected samples were measured using the ELISA method. The habitat was characterized to assess the ecological requirements and growth conditions of Tychonema. Tychonema mats and anatoxin-a were detected at several sampling sites throughout the entire study period. Toxin concentrations increased with the progression of the vegetation period and with flow direction, reaching values between 0 and 220.5 µg/L. Community composition differed among pelagic and benthic samples, with life zone and substrate condition being the most important factors. The results of this study highlight the importance of monitoring and understanding the factors determining occurrence and toxin production of both pelagic and benthic cyanobacteria due to their relevance for the health of humans and aquatic ecosystems. 相似文献
25.
26.
Cyclosporin A in the ocular fluids of uveitis patients following long-term systemic administration 总被引:1,自引:0,他引:1
Paolo Mora Uta Ceglarek Francesca Manzotti Laura Zavota Arturo Carta Raffaella Aldigeri Jelka G. Orsoni 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2008,246(7):1047-1052
BACKGROUND/AIMS: To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases. METHODS: Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples. CONCLUSION: LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake. 相似文献
27.
28.
Joss von Hadeln Ronja Hensgen Tobias Bockhorst Ronny Rosner Ronny Heidasch Uta Pegel Manuel Quintero Pérez Uwe Homberg 《The Journal of comparative neurology》2020,528(6):906-934
The central complex (CX) comprises a group of midline neuropils in the insect brain, consisting of the protocerebral bridge (PB), the upper (CBU) and lower division (CBL) of the central body and a pair of globular noduli. It receives prominent input from the visual system and plays a major role in spatial orientation of the animals. Vertical slices and horizontal layers of the CX are formed by columnar, tangential, and pontine neurons. While pontine and columnar neurons have been analyzed in detail, especially in the fruit fly and desert locust, understanding of the organization of tangential cells is still rudimentary. As a basis for future functional studies, we have studied the morphologies of tangential neurons of the CX of the desert locust Schistocerca gregaria. Intracellular dye injections revealed 43 different types of tangential neuron, 8 of the PB, 5 of the CBL, 24 of the CBU, 2 of the noduli, and 4 innervating multiple substructures. Cell bodies of these neurons were located in 11 different clusters in the cell body rind. Judging from the presence of fine versus beaded terminals, the vast majority of these neurons provide input into the CX, especially from the lateral complex (LX), the superior protocerebrum, the posterior slope, and other surrounding brain areas, but not directly from the mushroom bodies. Connections are largely subunit- and partly layer-specific. No direct connections were found between the CBU and the CBL. Instead, both subdivisions are connected in parallel with the PB and distinct layers of the noduli. 相似文献
29.
30.
Expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic adenocarcinoma: Correlation with microvessel density 总被引:6,自引:0,他引:6
Kasper HU Wolf H Drebber U Wolf HK Kern MA 《World journal of gastroenterology : WJG》2004,10(13):1918-1922
AIM: Cyclooxygenases (COX) are key enzymes for conversion of arachidonic acid to prostaglandins. Nitric oxide synthase (NOS) is the enzyme responsible for formation of nitric oxide. Both have constitutive and inducible isoforms. The inducible isoforms (iNOS and COX-2) are of great interest as regulators of tumor angiogenesis, tumorigenesis and inflammatory processes. This study was to clarify their role in pancreatic adenocarcinomas. METHODS: We investigated the immunohistochemical iNOS and COX-2 expression in 40 pancreatic ductal adenocarcinomas of different grade and stage. The results were compared with microvessel density and clinicopathological data. RESULTS: Twenty-one (52.5%) of the cases showed iNOS expression, 15 (37.5%) of the cases were positive for COX-2. The immunoreaction was heterogeneously distributed within the tumors. Staining intensity was different between the tumors. No correlation between iNOS and COX-2 expression was seen. There was no relationship with microvessel density. However, iNOS positive tumors developed more often distant metastases and the more malignant tumors showed a higher COX-2 expression. There was no correlation with other clinicopathological data. CONCLUSION: Approximately half of the cases expressed iNOS and COX-2. These two enzymes do not seem to be the key step in angiogenesis or carcinogenesis of pancreatic adenocarcinomas. Due to a low prevalence of COX-2 expression, chemoprevention of pancreatic carcinomas by COX-2 inhibitors can only achieve a limited success. 相似文献