全文获取类型
收费全文 | 5263篇 |
免费 | 351篇 |
国内免费 | 43篇 |
专业分类
耳鼻咽喉 | 163篇 |
儿科学 | 119篇 |
妇产科学 | 28篇 |
基础医学 | 714篇 |
口腔科学 | 81篇 |
临床医学 | 485篇 |
内科学 | 1107篇 |
皮肤病学 | 205篇 |
神经病学 | 567篇 |
特种医学 | 326篇 |
外科学 | 947篇 |
综合类 | 24篇 |
一般理论 | 4篇 |
预防医学 | 182篇 |
眼科学 | 63篇 |
药学 | 287篇 |
中国医学 | 8篇 |
肿瘤学 | 347篇 |
出版年
2024年 | 4篇 |
2023年 | 36篇 |
2022年 | 59篇 |
2021年 | 123篇 |
2020年 | 76篇 |
2019年 | 112篇 |
2018年 | 132篇 |
2017年 | 103篇 |
2016年 | 136篇 |
2015年 | 188篇 |
2014年 | 188篇 |
2013年 | 285篇 |
2012年 | 427篇 |
2011年 | 419篇 |
2010年 | 271篇 |
2009年 | 228篇 |
2008年 | 375篇 |
2007年 | 416篇 |
2006年 | 345篇 |
2005年 | 316篇 |
2004年 | 313篇 |
2003年 | 266篇 |
2002年 | 264篇 |
2001年 | 55篇 |
2000年 | 49篇 |
1999年 | 55篇 |
1998年 | 46篇 |
1997年 | 49篇 |
1996年 | 25篇 |
1995年 | 26篇 |
1994年 | 26篇 |
1993年 | 32篇 |
1992年 | 13篇 |
1991年 | 15篇 |
1990年 | 12篇 |
1989年 | 6篇 |
1988年 | 9篇 |
1987年 | 15篇 |
1986年 | 10篇 |
1985年 | 6篇 |
1984年 | 13篇 |
1983年 | 9篇 |
1982年 | 14篇 |
1981年 | 8篇 |
1980年 | 12篇 |
1979年 | 6篇 |
1977年 | 10篇 |
1976年 | 12篇 |
1975年 | 8篇 |
1960年 | 4篇 |
排序方式: 共有5657条查询结果,搜索用时 46 毫秒
51.
Jochen Wolffgramm 《Psychopharmacology》1990,101(2):233-239
To study the effects of different kinds of social deprivation on voluntary ethanol (ETOH) intake male Wistar rats were housed by (a) individual caging, (b) contact caging (partial social deprivation), and (c) group caging (four individuals per cage). In the latter condition the individuals were separated once a week from each other for 24 h. The rats simultaneously received water 5%, 10% and 20% ETOH for a period of 14 weeks. Additional control animals received water. Isolated individuals drank significantly more alcohol than group-housed or contact-caged rats. After a few days they preferred the 20% solution. Circadian measures revealed a discontinuous intake of high doses (> 0.5 g/kg/h) during short time periods. Contact-caged rats consumed much less ETOH, but both the preference for 20% ETOH and the circadian course of intake were similar to those occurring after isolation. ETOH intake of group-housed individuals was low. These individuals preferred the 5% solution and continuously consumed small ETOH doses. During the period of short-term isolation they drank even more ETOH than long-term isolated individuals. In contrast to the latter, the enhancement of intake decreased after some weeks. It is suggested that the differences between the housing groups not only reflect different degrees of isolation stress, but may also be explained by a contribution of different reinforcing or aversive psychotropic effects of ETOH. Reduction of isolation stress is probably most important in the situation of short term separation, whereas dose-dependent reinforcement via social stimulation or sedation may affect the drug taking behavior under the other social conditions. 相似文献
52.
Muhammad Daud Prasad Dasari Marion Adelfinger Daniela Langenhorst Jasmin Lother Dragana Slavkovic-Lukic Carsten Berges Michaela Kruhm Annette Galler Cathrin Schleussner Christian H. Luther Karl Alberter Anton Althammer Haroon Shaikh Niklas Pallmann Jochen Bodem Mohammed El-Mowafy Andreas Beilhack Marcus Dittrich Max S. Topp Peter F. Zipfel Niklas Beyersdorf 《European journal of immunology》2023,53(11):2250284
To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4+ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4+ T-cell recall responses. Therapeutically, CD4+ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4+ T cells with CaEno1 modulated host CD4+ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4+ T-cell responses. 相似文献
53.
Joseli Lannes-Vieira Jochen Gehrmann Georg W. Kreutzberg Hartmut Wekerle 《Acta neuropathologica》1994,87(5):435-442
We have investigated the T cell receptor (TCR) repertoire in the inflammatory infiltrates of T line-transferred experimental autoimmune encephalomyelitis (EAE) of the Lewis rats. Using a panel of TCR V-specific monoclonal antibodies (mAbs) and immunocytochemistry, we studied the nature of the T cells entering the central nervous system (CNS) after transfer of either myelin basic protein (MBP)-reactive, or MBP-reactive but non-encephalitogenic T cell lines. All the MBP-specific T cell lines predominantely used the V8.2 TCR chain. T cell lines specific for the tuberculin purified protein derivative (PPD), using TCR V genes different from V8.2, served as controls. We first studied the time course of T cells entering the CNS. In all recipient rats, small, but significant numbers of -TCR-expressing infiltrate cells appeared in the CNS within the first 24 h after T cell transfer. In animals injected with either type of MBP-reactive T cells, the early infiltrate cells were preferentially located within the parenchyma of the spinal cord, while in PPD T lineinjected rats, the lymphocytes were mostly found in the meninges. TCR V gene usage was examined on the peak of clinical disease. Six days after T cell transfer, the TCR repertoire used by infiltrating lymphocytes in general seemed to be highly diverse. None of the V isotypes examined (i.e. V8.2, V8.5 or V10) was used by a major population of the -TCR-positive T cells. A more detailed, quantitative analysis of individual infiltrate compartments revealed, however, a preferential accumulation of V8.2-positive T cells within the parenchyma. In contrast, perivascular infiltrating cells used V genes randomly. Our results confirm first that activated T lymphocytes enter the brain rapidly irrespective of their antigen specificity. Second, the data show that most of the perivascular infiltrate T cells in the acute EAE lesion are host-derived, recruited presumably from the recirculating T cell pool, while the encephalitogenic, V8.2-positive T cells preferentially persist within the parenchyma.Abbreviations
EAE
experimental autoimmune encephalomyelitis
-
MBP
myelin basic protein
-
TCL
T cell line
Supported by the Brazilian Research Council (CNPq) 相似文献
54.
Cyclosporine is a powerful immunosuppressant with a narrow therapeutic window and considerable inter- and intrapatient variability.
The pre-dose trough concentration (Cmin) is commonly used for therapeutic drug monitoring. With the new microemulsion (Neoral), intrapatient variability was reduced.
However, the usefulness of Neoral Cmin was questioned. Firstly, because of the improved and more-rapid absorption, accidental intake before blood sampling has a
greater impact on Cmin than with classic cyclosporine. Secondly, Cmin may be low despite high drug exposure, due to rapid clearance in children. A full pharmacokinetic (PK) profile with determination
of the area under the curve (AUC) is expensive and cumbersome, and therefore a search for an abbreviated AUC began. Here,
we present a retrospective analysis of 84 PK profiles from 78 pediatric renal transplant recipients. By analysis of rejection
episodes and toxicity, we estimated a target AUC above 5,000 ng×h/ml in the early post-transplant period and 3,900 ng×h/ml
beyond 100 days. The abbreviated AUC using the 2- and 6-h concentrations (C2 and C6) and a simple estimate derived from the
3-h concentration (C3) were equally well correlated with the AUC. From our data, we recommend a target C3 at approximately
800 ng/ml early after transplantation and 450–550 ng/ml beyond 100 days.
Received: 28 January 1998 / Revised: 10 June 1998 / Accepted: 15 June 1998 相似文献
55.
Christoph Kaiser Felix Bergel Ekkehard Doehring-Schwerdtfeger Hermann Feldmeier Jochen H. H. Ehrich 《Pediatric nephrology (Berlin, Germany)》1992,6(2):145-148
Semi-quantitative urinalysis with urine reagent strips (URS) for erythrocyturia (EU), leucocyturia (LU) and proteinuria (PU) was performed in Congolese and Sudanese school children withSchistosoma haematobium and/orS.mansoni infection. Quantitative urinalysis was performed on the same specimen using microscopy and a Neubauer counting chamber for EU and LU and the Coomassie blue dye-binding assay for PU. Microscopically detectable EU of more than 10 cells/l was found in 63% of all samples and LU of more than 20 cells/l was found in 60% of all samples. With the Coomassie blue method, PU of more than 150 mg/l was detected in 51% of all samples. URS gave positive results of grade 1–3 for EU in 69% of all samples, for LU in 63% of all samples and for PU in 66% of all samples. The sensitivity and specificity of URS compared with standard reference methods were as follows: EU 95% and 75%, LU 81% and 81% and PU 90% and 56%. When the results of all three test were combined, URS differentiated abnormal from normal urine specimens with a sensitivity of 94% and a specificity of 70%. Median quantitative results showed a good correlation with semiquantitative URS readings for all parameters, but there was a wide range of URS scores.We concluded that URS sensitively detect urinary abnormalities and thus may be used as a general screening method under field conditions when more specific methods cannot be performed. In the hospital laboratory,urine microscopy with a counting chamber would be preferred to URS as a sole method for EU and LU detection; URS is useful for the detection of PU in the tropical hospital laboratory where an appropriate quantitative method with a better specificity may not be available. 相似文献
56.
Prognostic impact of ANX7-GTPase in metastatic and HER2-negative breast cancer patients. 总被引:4,自引:0,他引:4
Meera Srivastava Lukas Bubendorf Mark Raffeld Christoph Bucher Jochen Torhorst Guido Sauter Cara Olsen Olli P Kallioniemi Ofer Eidelman Harvey B Pollard 《Clinical cancer research》2004,10(7):2344-2350
PURPOSE: ANX7-GTPase located on chromosome 10q21 is significantly altered and associated with hormone-refractory metastatic prostate cancers. Therefore, we investigated whether levels of ANX7 correlate with breast cancer progression and survival EXPERIMENTAL DESIGN: A diagnostic tumor tissue microarray containing 525 human breast tissue specimens at different stages of the disease was assayed for ANX7 using immunocytochemical methods with ANX7 monoclonal antibody. A separate prognostic tumor tissue microarray containing 553 human breast tissue specimens annotated with clinicopathological parameters was assayed for ANX7, HER2, estrogen receptor, progesterone receptor, and p53 protein. RESULTS: We report here for the first time that the expression of ANX7-GTPase is significantly enhanced and associated with the presence of metastatic disease (P < 0.0001) in the 525 human breast tissue specimens analyzed. Furthermore, using a separate 553 case retrospective prognostic tumor tissue microarray, we found that increased ANX7 expression is also significantly associated with poor overall patient survival (P < 0.014). This is particularly true when restricted to patients in whom the BRE clinical grade is 2 (P < 0.001) or for whom there is a lack of HER2 expression (P < 0.002). Finally, Cox regression analysis shows that as the expression of ANX7 rises, the probability of survival decreases by more than 10-fold for those patients with HER2-negative tumors. These latter patients represented 66% of the population affected with breast cancer in this study. CONCLUSIONS: High levels of ANX7 in tumor correlate strongly with poor survival of HER2-negative patients and the most aggressive forms of breast cancer. This is the first study to demonstrate that ANX7 antibody has the potential for development into an in vivo diagnostic and therapeutic tool. This simple and reliable immunohistochemical assay may therefore become an important biomarker for metastatic breast cancer diagnosis and management of HER2-negative breast tumor patients. 相似文献
57.
Adorján F Kovács Natascha D?bert Jochen Gaa Christian Menzel Klaus Bitter 《Journal of clinical oncology》2004,22(19):3973-3980
PURPOSE: To assess the impact of a diagnostic ladder including [(18)F]fluorodeoxyglucose positron emission tomography (PET) and lymphoscintigraphy guided sentinel node biopsy (LS/SNB) on neck treatment in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). PATIENTS AND METHODS: Prospectively, 62 patients with resectable T1-3 OOSCC underwent computed tomography (CT) and PET. Patients without neck uptake in PET were defined as cN0 and were accrued for LS/SNB. Results were correlated with histopathology. The traditional guidelines according to CT findings were compared to the actual regimen and the outcome. RESULTS: Sensitivity, specificity, validity, and positive and negative predictive value of PET versus CT were 72% v 89%, 82% v 77%, 79% v 80.5%, 62% v 61.5%, and 88% v 94.5% (not significant). Thirty-eight PET negative patients underwent LS/SNB. Sentinel lymph nodes were found in all 38 patients. Five patients had positive nodes (PET false-negatives) and underwent neck dissection (ND). Fifty-one neck sides in 36 patients who were CT-negative would have been treated with selective ND according to the guidelines, and at least 45 neck sides would have had to undergo extensive ND because of positive CT findings (96 of 124 neck sides). In contrast, PET in combination with LS/SNB spared 59 neck sides, and 41 of 124 neck sides actually underwent ND as a result of PET staging, LS/SNB, and intraoperative decision. After a median follow-up of 35 months, two patients (both cN+ve and pN+ve) suffered from neck relapses. CONCLUSION: Diagnostics using PET in combination with LS/SNB considerably reduced the number of extensive ND in OOSCC as compared to CT without locoregional hazard. 相似文献
58.
Torsten Haferlach Claudia Schoch Helmut L?ffler Winfried Gassmann Wolfgang Kern Susanne Schnittger Christa Fonatsch Wolf-Dieter Ludwig Christian Wuchter Brigitte Schlegelberger Peter Staib Albrecht Reichle Uschi Kubica Hartmut Eimermacher Leopold Balleisen Andreas Grüneisen Detlef Haase Carlo Aul Jochen Karow Eva Lengfelder Bernhard W?rmann Achim Heinecke Maria Cristina Sauerland Thomas Büchner Wolfgang Hiddemann 《Journal of clinical oncology》2003,21(2):256-265
PURPOSE: On the basis of cytomorphology according to the French-American-British (FAB) classification, we evaluated the prognostic impact of dysplastic features and other parameters in de novo acute myeloid leukemia (AML). We also assessed the clinical significance of the recently introduced World Health Organization (WHO) classification for AML, which proposed dysplasia as a new parameter for classification. PATIENTS AND METHODS: We analyzed prospectively 614 patients with de novo AML, all of whom were diagnosed by central morphologic analysis and treated within the German AML Cooperative Group (AMLCG)-92 or the AMLCG-acute promyalocytic leukemia study. RESULTS: Patients with AML M3, M3v, or M4eo demonstrated a better outcome compared with all other FAB subtypes (P <.001); no prognostic difference was observed among other FAB subtypes. The presence or absence of dysplasia failed to demonstrate prognostic relevance. Other prognostic markers, such as age, cytogenetics, presence of Auer rods, and lactate dehydrogenase (LDH) level at diagnosis, all showed significant impact on overall and event-free survival in univariate analyses (P <.001 for all parameters tested). However, in a multivariate analysis, only cytogenetics (unfavorable or favorable), age, and high LDH maintained their prognostic impact. Dysplasia was not found to be an independent prognostic parameter, but the detection of trilineage dysplasia correlated with unfavorable cytogenetics. CONCLUSION: Our results indicate that cytomorphology and classification according to FAB criteria are still necessary for the diagnosis of AML but have no relevance for prognosis in addition to cytogenetics. Our results suggest that the WHO classification should be further developed by using cytogenetics as the main determinant of biology. Dysplastic features, in particular, have no additional impact on predicting prognosis when cytogenetics are taken into account. 相似文献
59.
60.