全文获取类型
收费全文 | 2846篇 |
免费 | 141篇 |
国内免费 | 6篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 111篇 |
妇产科学 | 87篇 |
基础医学 | 394篇 |
口腔科学 | 70篇 |
临床医学 | 274篇 |
内科学 | 534篇 |
皮肤病学 | 16篇 |
神经病学 | 354篇 |
特种医学 | 134篇 |
外科学 | 532篇 |
综合类 | 24篇 |
一般理论 | 2篇 |
预防医学 | 113篇 |
眼科学 | 15篇 |
药学 | 139篇 |
中国医学 | 2篇 |
肿瘤学 | 166篇 |
出版年
2022年 | 23篇 |
2021年 | 36篇 |
2020年 | 29篇 |
2019年 | 26篇 |
2018年 | 44篇 |
2017年 | 40篇 |
2016年 | 43篇 |
2015年 | 56篇 |
2014年 | 77篇 |
2013年 | 129篇 |
2012年 | 141篇 |
2011年 | 157篇 |
2010年 | 101篇 |
2009年 | 90篇 |
2008年 | 146篇 |
2007年 | 150篇 |
2006年 | 132篇 |
2005年 | 142篇 |
2004年 | 121篇 |
2003年 | 133篇 |
2002年 | 136篇 |
2001年 | 89篇 |
2000年 | 66篇 |
1999年 | 77篇 |
1998年 | 42篇 |
1997年 | 26篇 |
1996年 | 29篇 |
1995年 | 26篇 |
1994年 | 24篇 |
1993年 | 20篇 |
1992年 | 62篇 |
1991年 | 52篇 |
1990年 | 55篇 |
1989年 | 44篇 |
1988年 | 58篇 |
1987年 | 53篇 |
1986年 | 35篇 |
1985年 | 53篇 |
1984年 | 21篇 |
1983年 | 24篇 |
1982年 | 12篇 |
1980年 | 11篇 |
1979年 | 17篇 |
1977年 | 9篇 |
1975年 | 10篇 |
1974年 | 13篇 |
1973年 | 14篇 |
1972年 | 12篇 |
1971年 | 16篇 |
1969年 | 13篇 |
排序方式: 共有2993条查询结果,搜索用时 15 毫秒
31.
Andreas Schalhorn Michael Kühl Gabriele Stupp-Poutot Volkmar Nüssler 《Cancer chemotherapy and pharmacology》1990,25(6):440-444
Summary After the use of d,1-folinic acid (d,1-CHO-THF), pharmacokinetic measurements should take into account 1-CHO-THF and its metabolite 1-methyltetrahydrofolic acid (1-CH3-THF) as well as d-CHO-THF. For this purpose, we developed a simple and rapid assay by combining reversed-phase HPLC to determine total levels of d,1-CHO-THF and CH3-THF and chiral HPLC to separate the biologically active 1-CHO-THF from the inactive d-CHO-THF. We investigated the pharmacokinetics after short-term infusion of 300 mg d,1-CHO-THF in ten healthy volunteers. With a mean of 56.5 min, 1-CHO-THF exhibits a rapid body clearance of 222 ml/min, about 60% of which is caused by metabolism to CH3-THF and 40%, by renal excretion. CH3-THF has a terminal half-life of 208 min and a total body clearance of 88.9 ml/min, which is essentially the same as the renal clearance. Due to the lower clearance of CH3-THF, its AUC (2,132 M × min) exceeds that of 1-CHO-THF (1445 M × min) by approximately 50%. In contrast to that of the reduced 1-folates, the total body and renal clearance of d-CHO-THF is very low, with values of 13.2 and 12.9 ml/min, respectively. This results in a very high AUC of 24, 269 M × min, which is higher by factors of 17 and 11 than those of 1-CHO-THF and CH3-THF, respectively. The implications of the distinct kinetics of the reduced 1-folates and d-CHO-THF for the efficacy of folinic acid/5-fluorouracil therapy and adequate protocols for the treatment of advanced colorectal cancer are discussed.Abbreviations CH2-THF
N-5,N-10-methylenetetnahydrofolic acid
- CH3-THF
N-5-methyltetrahydrofolic acid
- CHO-THF
N-5-formyltetrahydrofolic acid
- 5-FU
5-fluorouracil
- FBAL
-fluoro--alanine
- FUH2
dihydrofluorouracil
- FUPA
-fluoroureidopropionic acid
Dedicated to Prof. Dr. W. Wilmanns on the occasion of his 60th birthdayThis study was carried out with the support of the Lederle Company, Wolfratshausen 相似文献
32.
Significance of sagittal stability in knee prosthesis implantation--an analysis of 76 cases with unconstrained joint surface replacement 总被引:2,自引:0,他引:2
Pellengahr C Jansson V Dürr HR Refior HJ 《Zeitschrift für Orthop?die und ihre Grenzgebiete》1999,137(4):330-333
ISSUE: How does the sagittal stability influence the outcome in unconstrained knee arthroplasty? METHOD: In order to clarify this aspect, 76 arthroplasties (10 male, 66 female, 39x gonarthrosis, 37x rheumatoid arthritis) in 61 patients with unconstrained primary knee arthroplasty were examined with a mean follow-up of 4 years. The determined values were the HSS-Score, the Knee-Society-Score, the range of motion, the flexion contracture as well as the posterior and anterior drawer with the KT 1000. The laxity was defined as the sum of the anterior and posterior drawer. RESULTS: The mean values measured were 2.9 mm for the anterior drawer, 1.9 mm for the posterior drawer and 4.8 mm for the laxity. The total patient population reached 81.3 points in the Knee Score, 70.9 points in the Function-Score and 80.7 points in the HSS-Score. The medium range of motion was determined as 103.5 degrees, the medium flexion contracture as 3.5 degrees. For an anterior drawer of > 6 mm and a posterior drawer of < 1 mm the results deteriorated significantly. A laxity of 8-11 mm gave the best score results. CONCLUSION: An anterior drawer of < 6 mm, a posterior drawer of 2-5 mm and a laxity of 8-11 mm seem to be recommendable for unconstrained knee arthroplasty. 相似文献
33.
C C Jansson K Pohjanoksa J Lang S Wurster J M Savola M Scheinin 《European journal of pharmacology》1999,374(1):137-146
Transfected Chinese hamster ovary cells expressing human alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes were used to monitor alpha2-adrenoceptor-stimulated GTP hydrolysis. Incubation with 100 microM (-)-adrenaline resulted in stimulation of pertussis toxin-sensitive GTPase by 380% after activation of the alpha2A-subtype, by 320% after activation of the alpha2B-subtype and by 110% after activation of the alpha2C-subtype. The agonists dexmedetomidine, UK14,304 (5-bromo-6-[2-imidazoline-2-ylamino]quinoxaline) and oxymetazoline showed subtype-dependent efficacy. Dexmedetomidine was a full agonist at the alpha2B-subtype and a partial agonist at the alpha2A- and the alpha2C-subtypes. UK14,304 was a full agonist at the alpha2A-subtype and a partial agonist at the other two. Oxymetazoline showed strong partial agonism at the alpha2B-subtype (63% of adrenaline), but did not significantly activate the alpha2A- and the alpha2C-subtypes. These results agreed with cAMP accumulation experiments carried out with cell lines endogenously expressing the alpha2A-subtype (human erythroleukemia, HEL) or the alpha2B-subtype (neuroblastoma-glioma, NG108-15). The GTPase assay may thus provide a valuable tool for the identification of subtype-selective alpha2-adrenoceptor agonists. 相似文献
34.
Asperger's disorder 总被引:1,自引:0,他引:1
Volkmar FR Klin A Schultz RT Rubin E Bronen R 《The American journal of psychiatry》2000,157(2):262-267
35.
Local blood flow regulation in transplanted rat pancreatic islets: influence of adenosine, angiotensin II, and nitric oxide inhibition 总被引:3,自引:0,他引:3
BACKGROUND: Transplanted islets lack endothelial cells immediately after implantation and therefore depend on an adequate revascularization for their survival and function. However, the functional properties of the newly formed islet graft microvessels are largely unknown. This study aimed to investigate the blood flow regulation of transplanted pancreatic islets. METHODS: Pancreatic islets were syngeneically transplanted beneath the renal capsule of control and streptozotocin-diabetic rats. Blood flow measurements were performed 4 weeks later using laser-Doppler flowmetry. Adenosine (0.6 mg x kg(-1) x min(-1), angiotensin II (AT II; 0.17 microg x kg(-1) x min(-1)) and the nitric oxide synthase inhibitor NG-nitro-L-arginine (25 mg/ kg) were given to each animal. RESULTS: An increased basal blood flow and basal vascular conductance in the islet grafts, but not in the renal cortex, were seen in diabetic rats compared with control rats. Adenosine increased, and AT II decreased, the vascular conductance of the islet grafts in both nondiabetic and diabetic animals. A more pronounced circulatory response to AT II was observed in kidneys of diabetic animals, whereas there was no difference in the islet graft blood flow response between nondiabetic and diabetic animals. NG-Nitro-L-arginine decreased islet graft blood flow and vascular conductance in both nondiabetic and diabetic recipients, but the effect was more pronounced in the non-diabetic animals. CONCLUSIONS: Islet graft blood flow was influenced by adenosine, AT II, and nitric oxide inhibition in all animals. However, diabetic animals were less dependent on nitric oxide to maintain a basal blood flow in the islet graft. 相似文献
36.
Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. 总被引:2,自引:0,他引:2
Klaus Pantel Volkmar Müller Margherita Auer Nathalie Nusser Nadia Harbeck Stephan Braun 《Clinical cancer research》2003,9(17):6326-6334
Blood-borne distant metastasis is the leading cause of cancer-related death in breast cancer. The onset of this fundamental process can now be assessed in cancer patients using ultrasensitive immunocytochemical and molecular assays able to detect even single metastatic cells. Analyses of bone marrow (BM) samples show that disseminated cells are present in 20-40% of primary breast cancer patients without any clinical or histopathological signs of metastasis. The common homing of circulating breast cancer cells in BM is indicative for systemic tumor cell spread and predictive for growth of overt metastases in relevant organ sites such as bone, lung, or liver. Recent clinical studies involving more than 3000 breast cancer patients demonstrated that the presence of tumor cells in BM at primary diagnosis is an independent prognostic factor for unfavorable clinical outcome. To date, sampling of BM, however, is not a routine procedure in clinical management of breast cancer patients. Therefore, several research groups have developed sensitive assays for detection of circulating tumor cells in peripheral blood. Studies evaluating the clinical relevance of these blood assays are ongoing. Here, we will review the existing tumor cell assays and discuss their current clinical relevance and perspectives for the clinical management of breast cancer patients. 相似文献
37.
Rainov Nikolai G. Dobberstein Karl-Ulrich Bahn Hannes Holzhausen Hans-Jürgen Lautenschläger Christine Heidecke Volkmar Burkert Winfried 《Journal of neuro-oncology》1997,35(1):13-28
Despite the use of multimodal therapy, higher-grade glioma is stilluniformly fatal in the adult population. There is a considerable differencebetween the length of survival in each given patient, even within the sametumor type and malignancy grade group, suggesting that there are factorsthat might differentially influence outcome. To identify such factors, 107patients with anaplastic or malignant glioma were retrospectivelyinvestigated. Clinical parameters and paraclinical data on the p53, mdm2,and EGFR genes at the DNA or protein level were evaluated by univariateanalysis and Cox proportional hazards regression modeling. Kaplan-Meiersurvival estimation demonstrated that immunohistochemical positivity formdm2 protein in patients with anaplastic astrocytoma or with glioblastomamultiforme was associated with a shorter survival time (p = 0.02).P53 gene mutations and immunopositivity for the epidermal growth factorreceptor (EGFR) protein were not significantly related to poor prognosis.The Cox proportional hazards model revealed immunohistochemical positivityfor p53, mdm2, or for both of them, the presence of postoperativeirradiation, and the extent of surgical resection of tumor to be variablessignificantly associated with prolonged survival. EGFR overexpression, ageover 60 years, and Karnofsky performance score below 40 points did notsignificantly shorten survival time. In conclusion, the present studyidentified immunohistochemically detected mdm2-protein overexpression as astatistically significant negative prognostic parameter in patients bearinganaplastic or malignant glioma. Association analysis of variables revealed apossible correlation between mdm2 and p53, which is also consistent with thebiological interaction mode of both proteins in vivo. 相似文献
38.
Carlsson PO Andersson A Carlsson C Hellerström C Höglund E King A Källskog O Liss P Mattsson G Olsson R Palm F Sandler S Tyrberg B Jansson L 《Upsala journal of medical sciences》2000,105(2):107-123
Transplantation of pancreatic islets may provide a cure for type 1 diabetes. However, this treatment can currently be offered only to very few patients. To improve transplantation success we need to understand better the mechanisms of how the implanted islets survive, grow and/or maintain adequate function. We herein report on our studies to evaluate the factors responsible for the engraftment, i.e. revascularization, reinnervation etc., of transplanted islets and relate these factors to the metabolism and growth of the islets. Graft metabolism can be monitored by microdialysis probes that allow for the measurement of minute amounts of islet metabolites and hormonal products. Growth of the endocrine cells can be stimulated both in vitro before implantation and in vivo post-transplantation. Another problem is rejection of transplanted islets, which may be overcome by the microencapsulation of islets. The knowledge gained by the present studies will enable us to elucidate the optimal treatment of islets to ensure a maximal survival of the transplanted islets, and may be applied also to clinical islet transplantation. 相似文献
39.
40.
Dr. A. Jansson U. Wintergerst S. Bechtold B. H. Belohradsky 《Monatsschrift für Kinderheilkunde》2006,154(10):990-995
Systemic lupus erythematosus (SLE) is an autoimmune disorder which can affect every organ. Its etiopathogenesis is not fully understood, but animal models have demonstrated that B lymphocytes play an important role in the pathogenesis of affected organs. Severely ill patients may not respond to conventional immunosuppressive therapies. In such cases therapeutic options such as plasmapheresis, newer experimental therapies, or autologous stem cell therapy are applied with variable success. Especially for severely affected children safe therapeutic options are desperately needed. We report two children with therapy-refractory SLE who responded to rituximab – a genetically engineered monoclonal CD20 antibody. B-cell depletion with rituximab seems to be a promising therapy for refractory SLE. Compared to the severe side effects of immunosuppressive drugs, rituximab appears to be safer and should be considered for children with severe SLE. Controlled studies are needed. 相似文献