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   2601篇
  免费   198篇
  国内免费   23篇
耳鼻咽喉   21篇
儿科学   173篇
妇产科学   29篇
基础医学   285篇
口腔科学   65篇
临床医学   253篇
内科学   543篇
皮肤病学   27篇
神经病学   150篇
特种医学   506篇
外国民族医学   3篇
外科学   263篇
综合类   46篇
预防医学   168篇
眼科学   43篇
药学   136篇
中国医学   4篇
肿瘤学   107篇
  2022年   16篇
  2021年   42篇
  2020年   20篇
  2019年   29篇
  2018年   51篇
  2017年   38篇
  2016年   41篇
  2015年   52篇
  2014年   49篇
  2013年   89篇
  2012年   63篇
  2011年   92篇
  2010年   97篇
  2009年   81篇
  2008年   73篇
  2007年   75篇
  2006年   71篇
  2005年   55篇
  2004年   43篇
  2003年   48篇
  2002年   45篇
  2001年   32篇
  2000年   45篇
  1999年   47篇
  1998年   146篇
  1997年   128篇
  1996年   130篇
  1995年   101篇
  1994年   83篇
  1993年   87篇
  1992年   38篇
  1991年   33篇
  1990年   36篇
  1989年   79篇
  1988年   57篇
  1987年   60篇
  1986年   57篇
  1985年   60篇
  1984年   36篇
  1983年   39篇
  1982年   43篇
  1981年   21篇
  1980年   41篇
  1979年   19篇
  1978年   20篇
  1977年   21篇
  1976年   33篇
  1975年   28篇
  1973年   17篇
  1971年   20篇
排序方式: 共有2822条查询结果,搜索用时 281 毫秒
81.
Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.  相似文献   
82.
Control of cardiomyocyte cytosolic Ca2+ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca2+, Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca2+ channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca2+ levels promote the binding of a Ca2+/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca2+ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδB in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδC. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδB, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca2+ uptake and maintain cytosolic Ca2+ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.  相似文献   
83.
CD19 chimeric antigen receptor T (CAR T)-cell therapy with axicabtagene ciloleucel (axi-cel) for relapsed or refractory (R/R) large B-cell lymphoma (LBCL) may lead to durable remissions, however, prolonged cytopenias and infections may occur. In this single center retrospective study of 85 patients, we characterized immune reconstitution and infections for patients remaining in remission after axi-cel for LBCL. Prolonged cytopenias (those occurring at or after day 30 following infusion) were common with ≥grade 3 neutropenia seen in 21 of 70 (30%) patients at day 30 and persisting in 3 of 31 (9.7%) patients at 1 year. B cells were undetectable in 30 of 34 (88.2%) patients at day 30, but were detected in 11 of 19 (57.9%) at 1 year. Median immunoglobulin G levels levels reached a nadir at day 180. By contrast, CD4 T cells decreased from baseline and were persistently low with a median CD4 count of 155 cells/mL at 1 year after axi-cel (n=19, range: 33– 269). In total, 23 of 85 (27.1%) patients received intravenous immunoglobulins after axi-cel, and 34 of 85 (40%) received granulocyte-colony stimulating factor. Infections in the first 30 days occurred in 31 of 85 (36.5%) patients, of which 11 of 85 (12.9%) required intravenous antibiotics or hospitalization (“severe”) and were associated with cytokine release syndrome, neurotoxicity, tocilizumab use, corticosteroid use, and bridging therapy on univariate analyses. After day 30, seven severe infections occurred, with no late deaths due to infection. Prolonged cytopenias are common following axi-cel therapy for LBCL and typically recover with time. Most patients experience profound and prolonged CD4 T-cell immunosuppression without severe infection.  相似文献   
84.
BACKGROUND: Patients with irritable bowel syndrome (IBS) often report family members with similar symptoms, but family studies are lacking. We hypothesised that if there is familial aggregation, there would be an increased frequency of IBS in first degree relatives of IBS patients compared with relatives of controls (the patient's spouse). METHODS: A valid self report bowel disease questionnaire (BDQ) that recorded symptoms, the somatic symptom checklist (a measure of somatisation), and a family information form (FIF) to collect the names and addresses of all first degree relatives were mailed to two groups of patients and their spouses (patients attending an IBS educational programme and residents of Olmsted County, Minnesota, who had been coded as IBS on a database). A BDQ was then mailed to all first degree relatives of subjects identified from the FIF. IBS diagnosis in the relatives was based on the Manning criteria. RESULTS: The BDQ was sent to a total of 355 eligible relatives; 71% responded (73% relatives of patients, 67% relatives of spouses). Relatives were comparable in mean age, sex distribution, and somatisation score. IBS prevalence was 17% in patients' relatives versus 7% in spouses' relatives (odds ratio adjusted for age and sex 2.7 (95% confidence interval (CI) 1.2, 6.3)). When also adjusted for somatisation score, the odds ratio was reduced to 2.5 (95% CI 0.9, 6.7). CONCLUSIONS: Familial aggregation of IBS occurs, supporting a genetic or intrafamilial environment component, but this may be explained in part by familial aggregation of somatisation.  相似文献   
85.
When normal volunteers or patients with type I von Willebrand disease (VWD) are given desmopressin (DDAVP), a set of larger-than-normal (supranormal) von Willebrand factor (VWF) multimers, similar to those present in VWF-containing cells such as platelets megakaryocytes and endothelial cells, appear transiently in postinfusion plasma. In two kindreds with mild lifelong bleeding symptoms transmitted as an autosomal dominant trait, all ten symptomatic members (but none of the five asymptomatic members) had a supranormal multimeric structure for plasma VWF, apparently identical to that seen for postdesmopressin normal plasma. Plasma factor VIII coagulant activity (VIII:C), VWF antigen (VWF:Ag), ristocetin-induced platelet agglutination, and ristocetin cofactor (RiCof) activity were low. Platelet VWF:Ag and RiCof levels (tested for three patients only) were normal. Bleeding times were normal or slightly prolonged. The patients' platelet multimeric structure was the same as that for normal platelets. After desmopressin infusion the plasma VWF multimeric structure remained supranormal as for preinfusion plasma, with VIII:C VWF:Ag and RiCof increasing markedly over baseline values and disappearing at a normal rate. Examination of the VWF subunit composition from three of these patients indicated that proteolytic processing of their VWF did not differ from normal. This study describes the first variant of VWD with a supranormal multimeric structure.  相似文献   
86.
87.

Objective:

To investigate whether there was parity between treatment fields localized by radiographers and clinicians, by comparing geographical variations and hence determining the feasibility of a radiographer-led service.

Methods:

23 patients with metastatic spinal cord compression (MSCC) were prospectively sampled. Four radiographers not involved in the original planning performed localization on each patient. The 92 localizations that they determined were compared with the clinician-approved fields. Agreement was defined as ≤0.5 cm between field length, width and three isocentre co-ordinates. To be feasible, agreement was required in a minimum of 97% of the cases. The potential time saved with a radiographer-led approach was also recorded.

Results:

Agreement between clinicians and radiographers was 97.8%. For all field parameters, the average differences were <0.3 cm and were significantly different from the 0.5-cm median (p < 0.0001) that would establish no agreement using Wilcoxon signed-rank test. The average (range) delay awaiting clinician approval was 54 min (4–141 min).

Conclusion:

Strong agreement between radiographer and clinician localizations was established. It was also highlighted that time could be saved in the patient''s pathway by removing the need to wait for clinician approval. We believe this supports a radiographer-led service.

Advances in knowledge:

This article is novel, as it is the first known comparison between clinicians and radiographers in the localization of MSCC radiotherapy. These data show the feasibility of introducing radiographer-led practice and a methodology that could be potentially transferred to investigate the localization parity for other treatment sites.  相似文献   
88.

Background:

Hip resurfacing arthroplasty (HRA) is primarily indicated for young, active patients with disabling coxarthrosis who wish to remain active and return to sports after surgery. Relatively few prospective studies have assessed return to sporting activity and impact of gender and age on this.

Materials and Methods:

Seventy-nine consecutive patients treated with HRA were included. Patients were reviewed clinically and radiologically. Function was assessed using the modified University of California Los Angeles (UCLA) activity score. The Oxford, Harris and WOMAC hip scores were calculated.

Results:

Average age at the time of surgery was 54.9 years (range 34.5–73.6 years). Average preoperative and postoperative UCLA scores were 4 and 7.6 respectively. Patients were involved in 2 (0–4) sporting activities preoperatively and 2 (0–5) postoperatively. Preoperative and postoperative Oxford Hip Scores, Harris Hip Score and WOMAC scores were 40, 46 and 51 and 16, 94 and 3 respectively (P < 0.0001). Patients returned to sports at an average of 3 months postoperatively.

Conclusion:

Patients were able to return to sports by 3 months and perform the same number of activities at preoperative intensity. Activity levels are maintained up to the medium term with few complications.  相似文献   
89.

Introduction

Fast track methodology or enhanced recovery schemes have gained increasing popularity in perioperative care. While evidence is strong for colorectal surgery, its importance in gastric and oesophageal surgery has yet to be established. This article reviews the evidence of enhanced recovery schemes on outcome for this type of surgery.

Methods

A systematic literature search was conducted up to March 2014. Studies were retrieved and analysed using predetermined criteria.

Results

From 34 articles reviewed, 18 eligible studies were identified: 7 on gastric and 11 on oesophageal resection. Three randomised controlled trials, five case-controlled studies and ten case series were identified. The reported protocols included changes to each stage of the patient journey from pre to postoperative care. The specific focus following oesophageal resections was on early mobilisation, a reduction in intensive care unit stay, early drain removal and early (or no) contrast swallow studies. Following gastric resections, the emphasis was on reducing epidural anaesthesia along with re-establishing oral intake in the first three postoperative days and early removal of nasogastric tubes.In the papers reviewed, mortality rates following fast track surgery were 0.8% (9/1,075) for oesophageal resection and 0% (0/329) for gastric resection. The reported morbidity rate was 16.5% (54/329) following gastric resection and 38.6% (396/1,075) following oesophageal resection. Length of stay was reduced in both groups compared with conventional recovery groups in comparative studies.

Conclusions

The evidence for enhanced recovery schemes following gastric and oesophageal resection is weak, with only three (low volume) published randomised controlled trials. However, the enhanced recovery approach appears safe and may be associated with a reduction in length of stay.  相似文献   
90.
Sugi  T; McIntyre  JA 《Blood》1995,86(8):3083-3089
Demonstration of autoimmune antiphospholipid antibodies (aPA) to negatively charged phospholipids (PL) in an enzyme-linked immunosorbent assay (ELISA) requires the presence of certain phospholipid-binding plasma proteins, eg, beta 2-glycoprotein I. We found a requirement for plasma against the electrically neutral or zwitterionic phospholipid, phosphatidylethanolamine (PE). Two of these PE-binding plasma proteins were identified as high molecular weight kininogen (HMWK) and low molecular weight kininogen (LMWK). We studied anti-PE antibody (aPE) seropositive plasma from 13 patients with SLE and/or recurrent spontaneous abortions by using partially purified kininogens and kininogen binding proteins from adult bovine serum isolated by carboxymethyl (CM)-papain affinity chromatography. Eleven of 13 sera recognized a kininogen-PE complex and/or a kininogen-binding protein- kininogen-PE complex. Some aPE-positive patient sera were shown to recognize highly purified HMWK and LMWK by ELISA only when the kininogens were presented on a PE substrate. These aPE sera did not recognize PE, HMWK, or LMWK when they were presented independently as the sole antigens on the ELISA plates. Other aPE-positive sera that did not react with PE-bound HMWK or LMWK reacted with the CM-papain column eluate when it was bound to PE, which suggests that these aPE recognize factor XI or prekallikrein, which normally bind to HMWK. The aPE ELISA reactivity of two patient sera were inhibited by preincubation of the CM-papain column eluate in the ELISA plate. These data show that most aPE are not specific for PE but require the presence of certain PL- binding plasma proteins that are kininogens or proteins in complex with kininogens. Our studies indicate that aPE bind to different plasma proteins than those implicated in anionic PL, aPA ELISA reactivity.  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