首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   6690篇
  免费   347篇
  国内免费   32篇
耳鼻咽喉   30篇
儿科学   80篇
妇产科学   87篇
基础医学   1004篇
口腔科学   57篇
临床医学   612篇
内科学   1240篇
皮肤病学   146篇
神经病学   749篇
特种医学   386篇
外科学   1127篇
综合类   19篇
一般理论   1篇
预防医学   234篇
眼科学   132篇
药学   479篇
中国医学   8篇
肿瘤学   678篇
  2023年   29篇
  2022年   60篇
  2021年   91篇
  2020年   74篇
  2019年   102篇
  2018年   123篇
  2017年   118篇
  2016年   155篇
  2015年   156篇
  2014年   207篇
  2013年   271篇
  2012年   369篇
  2011年   456篇
  2010年   267篇
  2009年   277篇
  2008年   435篇
  2007年   480篇
  2006年   448篇
  2005年   486篇
  2004年   462篇
  2003年   459篇
  2002年   401篇
  2001年   117篇
  2000年   62篇
  1999年   88篇
  1998年   94篇
  1997年   78篇
  1996年   52篇
  1995年   49篇
  1994年   48篇
  1993年   47篇
  1992年   37篇
  1991年   31篇
  1990年   26篇
  1989年   28篇
  1988年   30篇
  1987年   16篇
  1986年   15篇
  1985年   25篇
  1984年   19篇
  1983年   17篇
  1982年   21篇
  1981年   23篇
  1980年   20篇
  1979年   19篇
  1978年   23篇
  1977年   22篇
  1976年   26篇
  1975年   15篇
  1973年   16篇
排序方式: 共有7069条查询结果,搜索用时 15 毫秒
61.
Polymorphisms of genes coding for DNA repair can affect lung cancer risk. A common single nucleotide (-4) G-to-A polymorphism was identified previously in the 5' untranslated region of the XPA gene. In a case-control study in European Caucasians, the influence of this polymorphism on primary lung cancer risk overall and according to histologic subtypes was investigated. Four hundred sixty-three lung cancer cases (including 204 adenocarcinoma and 212 squamous cell carcinoma) and 460 tumor-free hospital controls were investigated using PCR amplification and melting point analysis of sequence-specific hybridization probes. Odds ratios (OR) were calculated by multiple logistic regression analysis adjusting for age, gender, smoking habits, and occupational exposure and showed a slightly enhanced risk for all lung cancer cases as well as for squamous cell carcinoma and adenocarcinoma cases. Gene-environment interactions were analyzed with respect to smoking and occupational exposure. A nearly 3-fold increased risk for adenocarcinoma associated with the XPA AA genotype was observed for occupationally exposed individuals (OR, 2.95; 95% confidence interval, 1.42-6.14) and for heavy smokers (OR, 2.52; 95% confidence interval, 1.17-5.42). No genotype-dependent increase in OR was found for nonexposed individuals or those smoking <20 pack-years. The significant effect of the XPA polymorphism in heavy smokers and occupationally exposed individuals suggests an important gene-environment interaction for the XPA gene. The underlying mechanisms as to why AA homozygotes are predisposed to lung adenocarcinoma and which specific carcinogens are involved remains to be determined.  相似文献   
62.
PURPOSE: Current combination treatment strategies in malignancy are designed to evaluate the use of cytotoxic drugs and antiangiogenic agents. Endostatin, a fragment of collagen XVIII, specifically inhibits proliferation, migration, and differentiation of endothelial cells in vitro as well as angiogenesis and tumor progression in in vivo models. In this study, we determine the antitumor effect of rhEndostatin administered alone or in combination with Adriamycin against established orthotopic murine mammary carcinoma. EXPERIMENTAL DESIGN: Mice bearing orthotopically established DA-3 mammary adenocarcinoma tumors received varying doses of rhEndostatin alone and in combination with Adriamycin to assess tumor growth inhibition. Additional studies of this in vivo combination included a determination of Adriamycin-induced cardiotoxicity and in vitro effects on human umbilical vein endothelial cell proliferation and cord formation. RESULTS: For single-agent activity, optimal tumor growth inhibition was observed after s.c. administration of 50 mg/kg/day rhEndostatin or 5 mg/kg Adriamycin injected i.v. every 4 days. Combination of Adriamycin with optimal or suboptimal doses of rhEndostatin resulted in synergistic inhibition of DA-3 tumor growth. Importantly, unlike other antiangiogenic agents, rhEndostatin did not exacerbate the cardiotoxicity of Adriamycin. The synergistic interaction between rhEndostatin and Adriamycin was also observed in vitro for inhibition of human umbilical vein endothelial cell proliferation and inhibition of cord formation. CONCLUSIONS: These data suggest that the synergy observed with rhEndostatin in combination with Adriamycin is exerted at the level of the endothelial cell and can result in enhanced tumor growth inhibition. The potential benefit of Adriamycin used in combination with rhEndostatin is being considered for clinical evaluation.  相似文献   
63.
PURPOSE: To define patients and tumor characteristics as well as therapy results, patients with pelvic osteosarcoma who were registered in the Cooperative Osteosarcoma Study Group (COSS) were analyzed. PATIENTS AND METHODS: Sixty-seven patients with a high-grade pelvic osteosarcoma were eligible for this analysis. Fifteen patients had primary metastases. All patients received chemotherapy according to COSS protocols. Thirty-eight patients underwent limb-sparing surgery, 12 patients underwent hemipelvectomy, and 17 patients did not undergo definitive surgery. Eleven patients received irradiation to the primary tumor site: four postoperatively and seven as the only form of local therapy. RESULTS: Local failure occurred in 47 of all 67 patients (70%) and in 31 of 50 patients (62%) who underwent definitive surgery. Five-year overall survival (OS) and progression-free survival rates were 27% and 19%, respectively. Large tumor size (P =.0137), primary metastases (P =.0001), and no or intralesional surgery (P <.0001) were poor prognostic factors. In 30 patients with no or intralesional surgery, 11 patients with radiotherapy had better OS than 19 patients without radiotherapy (P =.0033). Among the variables, primary metastasis, large tumor, no or intralesional surgery, no radiotherapy, existence of primary metastasis (relative risk [RR] = 3.456; P =.0009), surgical margin (intralesional or no surgical excision; RR = 5.619; P <.0001), and no radiotherapy (RR = 4.196; P =.0059) were independent poor prognostic factors. CONCLUSION: An operative approach with wide or marginal margins improves local control and OS. If the surgical margin is intralesional or excision is impossible, additional radiotherapy has a positive influence on prognosis.  相似文献   
64.
BACKGROUND AND PURPOSE: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals--the so-called Brussels guidelines from Grégoire et al., and the so-called Rotterdam guidelines from Nowak et al.--emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. MATERIALS AND METHODS: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. RESULTS AND CONCLUSIONS: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described.  相似文献   
65.
PURPOSE: To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT). PATIENTS AND METHODS: From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II. RESULTS: Pathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%. CONCLUSION: Even with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary.  相似文献   
66.
Dietary-induced changes in tissue levels of polyunsaturated fatty acids modify inflammatory reactions through changes in the synthesis of lipid and peptide mediators of inflammation. Four semipurified 20% fat diets, based on beef tallow (BT), safflower oil (SFO), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were provided. The DHA and EPA ratios of the (n-3) fatty acid-based diets were 1.1 and 3.4, respectively. The effect of prefeeding diets differing in EPA to DHA ratios prior to the induction of streptococcal cell wall (SCW) arthritis in female Lew/SSN rats was examined. Weanling rats were fed diets for 5 wk before arthritis induction and 5 wk post-arthritis induction. Footpad thickness, hock circumference, plasma and macrophage fatty acids and histological assessment were compared. There were no differences in food intake and final body weights among the groups. Footpad inflammation, reported as percentage change (adjusted for growth) was greatest for rats fed the BT-based diet, intermediate in those fed the SFO-based diet and least for the rats fed the EPA- and DHA-based diets (P < 0.05). Macrophage phospholipids revealed cellular incorporation of EPA and DHA from the fish-oil based diets which modified lipid and peptide mediators of inflammation. Histological sections of rat hocks ranked by severity of arthritis-related changes suggested that the SFO- and EPA-based diets were more successful in ameliorating the destructive arthritic phase in hock joints than the BT- and DHA-based diets (P = 0.09) in this model of arthritis. The course of SCW-induced arthritis can be altered by diet-induced changes in macrophage fatty acid composition. The EPA-based diet is more effective in suppression of inflammation than the DHA-based diet.  相似文献   
67.
In this report an attempt has been made to discuss some of the issues pertinent to myelofibrosis complicating chronic myeloproliferative disorders (CMPDs) that are significantly associated with megakaryocyte function. In this context, biochemical, clinical and particularly morphological features were reviewed. Morphological findings based on elaborate techniques were in keeping with the assumption that in chronic myeloid leukemia (1) the number of CD61-positive megakaryocytes, and in particular their precursors were the parameters most closely associated with myelofibrosis (2) an increased content of reticulin fibers in follow-up biopsies significantly correlated with laboratory data indicative of a high tumor burden (anemia, peripheral blasts, hepatosplenomegaly) and thus a more advanced stage of the disease process (3) even a slight increase in reticulin, i.e. doubling of the normal fiber density was associated with a worse prognosis independent of therapeutic regimens given (4) Dynamics of myelofibrosis was significantly influenced by treatment. In this context, calculation of the myelofibrosis progression index (MPI) revealed a higher score following interferon therapy compared with busulfan. In addition, in idiopathic myelofibrosis (5) the evolution of myelofibrosis was unpredictable and according to the MPI, progression occurred at a relatively low rate (6) proliferation and dilatation of sinusoids accompanying intravascular hematopoiesis and collagen type IV deposits were predominant features in later (fibro-osteosclerotic) stages in the course of disease (7) transmural migration of megakaryocytes demonstrated by three dimensional reconstruction revealed a mole-like tunneling through the thickened sinusoidal wall. A very careful assessment of the numerous correlations between bone marrow features and laboratory data will allow clinicians and pathologists to gain a better insight into the mutual relationships between hematological and morphological findings in CMPDs.  相似文献   
68.
(Nutr Diet 2005;62:130–137) Objective: To determine the acute and chronic effects of low doses of long chain (LC) n‐3 polyunsaturated fatty acids (PUFA) on plasma LC n‐3 PUFA levels. Design: In the acute study, six healthy omnivores, avoiding fish meals on the day prior to the study, provided a fasting blood sample initially and post prandially at four hours. In the chronic study, 12 healthy subjects provided a fasting blood sample at baseline and three weeks after daily consumption of the test food. Main outcome measures: Plasma non‐esterified fatty acid and phospholipid LC n‐3 PUFA composition. Statistical analysis: Differences in plasma non‐esterified fatty acids and phospholipid LC n‐3 PUFA. A pre‐ and post‐consumption of the test food were assessed using paired t‐tests (spss ). Results: The acute study demonstrated that a low dose of LC n‐3 PUFA (25% eicosapentaenoic acid and 75% docosahexaenoic acid) significantly increased eicosapentaenoic acid levels in plasma of human subjects postprandially from 0.30% to 0.42% of total non‐esterified fatty acids, a per cent change of 39% (P < 0.05). The chronic study demonstrated a significant increase in total n‐3 phospholipids from zero weeks (5.48% of total fatty acids) to three weeks (7.92% of total fatty acids), representing a per cent increase of 44% (P = 0.006). The n‐6 to n‐3 ratio of LC PUFA phospholipids demonstrated a significant reduction from 5.1 at zero weeks to 4.07 at three weeks, representing a reduction of 20% (P = 0.006). Conclusions: These findings demonstrate the bioavailability of LC n‐3 PUFA consumed as a low‐fat omega‐3‐enriched luncheon meat.  相似文献   
69.
运用彗星试验检测麝香酮对苯并(a)芘致DNA损伤的影响   总被引:1,自引:0,他引:1  
[目的]研究麝香酮在体内试验条件下 ,对苯并(a)芘致小鼠肝和肺细胞核DNA损伤的影响。[方法]SENCAR雄性成年小鼠灌胃 ,分别单独给予苯并(a)芘125、250、500mg/(kg·bw·d)和用麝香酮250、500mg/(kg·bw·d)预处理后再给予苯并(a)芘125mg/(kg·bw·d) ,处死动物后分离小鼠肝和肺组织细胞核做彗星测试 ,采用CCD成像分析系统分析彗星 ,取尾相 (olivertailmoment,OTM)值判断DNA损伤强度。[结果]苯并(a)芘各浓度组均出现小鼠肝和肺细胞OTM值的明显增加 ,高浓度麝香酮[500mg/(kg·bw·d)]可引起小鼠肝细胞OTM值的轻度增加。用高浓度麝香酮预处理小鼠后再给予苯并(a)芘 ,所观察到的肝、肺的DNA损伤 (肝OTM值为7.6、肺为11)较之苯并(a)芘单独染毒引起的DNA损伤(肝OTM值为5.1、肺为6.9)增加更明显。[结论]麝香酮能明显增强苯并(a)芘所致的DNA损伤作用  相似文献   
70.
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   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号