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41.
David C. Johnson Steven S. Raman Sohrab A. Mirak Lorna Kwan Amirhossein M. Bajgiran William Hsu Cleo K. Maehara Preeti Ahuja Izak Faiena Aydin Pooli Amirali Salmasi Anthony Sisk Ely R. Felker David S.K. Lu Robert E. Reiter 《European urology》2019,75(5):712-720
Background
Multiparametric magnetic resonance imaging (mpMRI) undoubtedly affects the diagnosis and treatment of localized prostate cancer (CaP). However, clinicians need a better understanding of its accuracy and limitations in detecting individual CaP foci to optimize management.Objective
To determine the per-lesion detection rate for CaP foci by mpMRI and identify predictors of tumor detection.Design, setting, and participants
We carried out a retrospective analysis of a prospectively managed database correlating lesion-specific results from mpMRI co-registered with whole-mount pathology (WMP) prostatectomy specimens from June 2010 to February 2018. Participants include 588 consecutive patients with biopsy-proven CaP undergoing 3-T mpMRI before radical prostatectomy at a single tertiary institution.Outcome measurements and statistical analysis
We measured mpMRI sensitivity in detecting individual CaP and clinically significant (any Gleason score ≥7) CaP foci and predictors of tumor detection using multivariate analysis.Results and limitations
The final analysis included 1213 pathologically confirmed tumor foci in 588 patients with primarily intermediate- (75%) or high-risk (12%) CaP. mpMRI detected 45% of all lesions (95% confidence interval [CI] 42–47%), including 65% of clinically significant lesions (95% CI 61–69%) and nearly 80% of high-grade tumors. Some 74% and 31% of missed solitary and multifocal tumors, respectively, were clinically significant. The majority of missed lesions were small (61.1% ≤1 cm); 28.3% were between 1 and 2 cm, and 10.4% were >2 cm. mpMRI missed at least one clinically significant focus in 34% of patients overall, and in 45% of men with multifocal lesions. On multivariate analysis, smaller, low-grade, multifocal, nonindex tumors with lower prostate-specific antigen density were more likely to be missed. Limitations include selection bias in a prostatectomy cohort, lack of specificity data, an imperfect co-registration process, and uncertain clinical significance for undetected lesions.Conclusions
mpMRI detects less than half of all and less than two-thirds of clinically significant CaP foci. The moderate per-lesion sensitivity and significant proportion of men with undetected tumor foci demonstrate the current limitations of mpMRI.Patient summary
Magnetic resonance imaging of the prostate before surgical removal for prostate cancer finds less than half of all individual prostate cancer tumors. Large, solitary, aggressive tumors are more likely to be visualized on imaging. 相似文献42.
Sevan Komshian Alik Farber Virendra I. Patel Philip P. Goodney Marc L. Schermerhorn Elizabeth A. Blazick Douglas W. Jones Denis Rybin Gheorghe Doros Jeffrey J. Siracuse 《Journal of vascular surgery》2019,69(2):405-413
Objective
Although endovascular repair of abdominal aortic aneurysms (AAAs) has been demonstrated to have favorable outcomes, not all cohorts of patients with AAA fare equally well. Our goal was to investigate perioperative and 1-year outcomes in patients with end-stage renal disease (ESRD) on dialysis, who have traditionally fared worse after vascular interventions, to assess how ESRD affects outcomes in a large modern cohort of endovascular aneurysm repair (EVAR) patients.Methods
The Vascular Quality Initiative database was queried for all patients undergoing EVAR from 2010 to 2017. ESRD patients were compared with patients not on dialysis. Propensity-matched scoring and multivariable analysis were used to isolate the effects of ESRD.Results
Of 28,683 EVARs identified, there were 321 (1.12%) patients with ESRD on dialysis. Patients with ESRD had no difference in presenting AAA size (57.5 ± 12.7 mm vs 56.7 ± 17.2 mm; P = .44); however, they had more urgent/emergent repairs (20.6% vs 13.6%; P = .002) than those without ESRD. ESRD patients were more often younger, nonwhite, and nonobese and less likely to have commercial insurance (P < .05). ESRD patients more often had hypertension, coronary artery disease, congestive heart failure, previous lower extremity bypass, aneurysm repair, and carotid interventions (P < .05). There was no difference in the rate of concomitant procedures. Matching based on demographics, comorbidities, and operative details showed that ESRD patients had longer hospital length of stay (4.8 ± 9.4 days vs 4.1 ± 12.6 days; P = .026) and higher 30-day mortality (7% vs 2.4%; P < .001). There was no difference in cardiac, pulmonary, lower extremity, bowel, and stroke complications or return to the operating room. On multivariable analysis, ESRD was associated with 30-day mortality (odds ratio, 4.1; 95% confidence interval, 2.6-6.7; P < .001). Of the 24,750 elective EVARs, 1.04% had ESRD on dialysis. Matched data for elective EVAR show increased postoperative length of stay, hospital mortality, and 30-day mortality for ESRD patients on dialysis compared with those who are not. There was no association with postoperative myocardial infarction or pulmonary complications. At 1 year, patients with ESRD on dialysis had worse survival (78% vs 94%; P < .001), and ESRD was associated with higher mortality (hazard ratio, 3.3; 95% confidence interval, 2.5-4.2; P < .001).Conclusions
Among patients undergoing EVAR, ESRD is independently associated with higher perioperative and 1-year mortality despite not being associated with higher postoperative complications. This should be taken into account during informed consent for EVAR and risk-benefit considerations in this high-risk population, particularly for elective repair. 相似文献43.
Anthony J. Bleyer Vincent A. Scavo Samuel E. Wilson Barry J. Browne Brian L. Ferris C. Keith Ozaki Timmy Lee Eric K. Peden Bradley S. Dixon Rick Mishler Timothy P. O&#x;Connor Kendrah Kidd Steven K. Burke 《Journal of vascular surgery》2019,69(2):507-515
Objective
Arteriovenous fistulas created in patients with chronic kidney disease often lose patency and fail to become usable. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in promoting radiocephalic fistula patency and use for hemodialysis.Methods
PATENCY-1 was a double-blind, placebo-controlled trial that enrolled 349 patients on or approaching hemodialysis and being evaluated for radiocephalic arteriovenous fistula creation. Of these, 313 were randomized and 311 treated. Patients were assigned to vonapanitase (n = 210) or placebo (n = 103). The study drug solution was applied topically to the artery and vein for 10 minutes immediately after fistula creation. The primary and secondary end points were primary patency (time to first thrombosis or corrective procedure) and secondary patency (time to abandonment). Tertiary end points included use of the fistula for hemodialysis, fistula maturation by ultrasound, and procedure rates.Results
The Kaplan-Meier estimates of 12-month primary patency were 42% (95% confidence interval [CI], 35-49) and 31% (95% CI, 21-42) for vonapanitase and placebo (P = .25). The Kaplan-Meier estimates of 12-month secondary patency were 74% (95% CI, 68-80) and 61% (95% CI, 51-71) for vonapanitase and placebo (P = .048). The proportions of vonapanitase and placebo patients were 39% and 25% (P = .035) with unassisted use for hemodialysis and 64% and 44% (P = .006) with unassisted plus assisted use.Conclusions
Vonapanitase treatment did not significantly improve primary patency but was associated with increased secondary patency and use for hemodialysis. Further research is needed to evaluate these end points. 相似文献44.
S. Kim M.J. Graham R.G. Lee L. Yang S. Kim V. Subramanian J.D. Layne L. Cai R.E. Temel D. Shih A.J. Lusis J.A. Berliner S. Lee 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(3):306-315
Background and aims
Heparin-binding EGF-like growth factor (HB-EGF) is a representative EGF family member that interacts with EGFR under diverse stress environment. Previously, we reported that the HB-EGF-targeting using antisense oligonucleotide (ASO) effectively suppressed an aortic aneurysm in the vessel wall and circulatory lipid levels. In this study, we further examined the effects of the HB-EGF ASO administration on the development of hyperlipidemia-associated atherosclerosis using an atherogenic mouse model.Methods and results
The male and female LDLR deficient mice under Western diet containing 21% fat and 0.2% cholesterol content were cotreated with control and HB-EGF ASOs for 12 weeks. We observed that the HB-EGF ASO administration effectively downregulated circulatory VLDL- and LDL-associated lipid levels in circulation; concordantly, the HB-EGF targeting effectively suppressed the development of atherosclerosis in the aorta. An EGFR blocker BIBX1382 administration suppressed the hepatic TG secretion rate, suggesting a positive role of the HB-EGF signaling for the hepatic VLDL production. We newly observed that there was a significant improvement of the insulin sensitivity by the HB-EGF ASO administration in a mouse model under the Western diet as demonstrated by the improvement of the glucose and insulin tolerances.Conclusion
The HB-EGF ASO administration effectively downregulated circulatory lipid levels by suppressing hepatic VLDL production rate, which leads to effective protection against atherosclerosis in the vascular wall. 相似文献45.
P. Mendogni S. Henchi L.C. Morlacchi D. Tosi M. Nosotti P. Tarsia A.I. Gregorini L. Rosso 《Transplantation proceedings》2019,51(1):194-197
Background
Solid organ transplantation is associated with a higher risk of Epstein-Barr virus (EBV)–related lymphoproliferative disease due to immunosuppressive regimen. Little evidence is currently available on post-transplant lymphoproliferative disorders (PTLDs) in the lung transplant (LuTx) setting, particularly in cystic fibrosis (CF) recipients.Methods
We retrospectively analyzed all the cases of PTLDs that occurred in our LuTx center between January 2015 and December 2017. We reviewed clinical and radiologic data, donor and recipient EBV serostatus, immunosuppressive therapy, histologic data, and follow-up of these patients.Results
A total of 77 LuTxs were performed at our center in the study period; 39 (50.6%) patients had CF; 4 developed EBV-related PTLDs. They were all young (17–26 years) CF patients with high serum EBV DNA load. Disease onset was within the first 3 months after LuTx. In 3 cases presentation was associated with fever and infection-like symptoms, whereas in 1 case radiologic suspicion arose unexpectedly from a CT scan performed for different clinical reasons. Diagnosis was reached through lung biopsy in all cases. All patients received rituximab,?cyclophosphamide, doxorubicin hydrochloride (hydroxydaunomycin), vincristine sulfate (Oncovin), and prednisone with variable response and complications.Conclusion
In our experience, the early development of EBV-related PTLD was a highly aggressive, life-threatening condition, which exclusively affected young CF patients in the early post-transplant period. The rate of this complication was relatively high in our population.Diagnosis with lung biopsy is crucial in all suspected cases and regular monitoring of EBV DNA levels is of utmost importance given the high correlation with PTLDs in patients at increased risk. 相似文献46.
M. Iachina P.M. Ljungdalh R.G. Sørensen L. Kaerlev J. Blaakær O. Trosko N. Qvist B.M. Nørgård 《Clinical oncology (Royal College of Radiologists (Great Britain))》2019,31(2):115-123
Aims
To examine the influence of pre-existing psychiatric disorder on the choice of treatment in patients with gynaecological cancer.Materials and methods
The analyses were based on all patients who underwent surgical treatment for endometrial, ovarian or cervical cancer who were registered in the Danish Gynecological Cancer Database in the years 2007–2014 (3059 patients with ovarian cancer, 5100 patients with endometrial cancer and 1150 with cervical cancer). Logistic regression model and Cox regression model, adjusted for relevant confounders, were used to estimate the effect of pre-existing psychiatric disorder on the course of cancer treatment. Our outcomes were (i) presurgical oncological treatment, (ii) macroradical surgery for patients with ovarian cancer, (iii) radiation/chemotherapy within 30 days and 100 days after surgery and (iv) time from surgery to first oncological treatment.Results
In the group of patients with ovarian cancer, more patients with a psychiatric disorder received macroradical surgery versus patients without a psychiatric disorder, corresponding to an adjusted odds ratio of 1.24 (95% confidence interval 0.62–2.41) and the chance for having oncological treatment within 100 days was odds ratio = 1.26 (95% confidence interval 0.77–2.10). As for patients with endometrial cancer, all outcome estimates were close to unity. The adjusted odds ratio for oncological treatment within 30 days after surgery in patients with cervical cancer with a history of psychiatric disorder was 0.20 (95% confidence interval 0.03–1.54).Conclusions
We did not find any significant differences in the treatment of ovarian and endometrial cancer in patients with pre-existing psychiatric diagnoses. When it comes to oncological treatment, we suggest that increased attention should be paid to patients with cervical cancer having a pre-existing psychiatric diagnosis. 相似文献47.
48.
Warren Fiskus Christopher P. Mill Behnam Nabet Dimuthu Perera Christine Birdwell Taghi Manshouri Bernardo Lara Tapan M. Kadia Courtney DiNardo Koichi Takahashi Naval Daver Prithviraj Bose Lucia Masarova Naveen Pemmaraju Steven Kornblau Gautam Borthakur Guillermo Montalban-Bravo Guillermo Garcia Manero Sunil Sharma Matthew Stubbs Xiaoping Su Michael R. Green Cristian Coarfa Srdan Verstovsek Joseph D. Khoury Christopher R. Vakoc Kapil N. Bhalla 《Blood cancer journal》2021,11(5)
There is an unmet need to overcome nongenetic therapy-resistance to improve outcomes in AML, especially post-myeloproliferative neoplasm (MPN) secondary (s) AML. Studies presented describe effects of genetic knockout, degradation or small molecule targeted-inhibition of GFI1/LSD1 on active enhancers, altering gene-expressions and inducing differentiation and lethality in AML and (MPN) sAML cells. A protein domain-focused CRISPR screen in LSD1 (KDM1A) inhibitor (i) treated AML cells, identified BRD4, MOZ, HDAC3 and DOT1L among the codependencies. Our findings demonstrate that co-targeting LSD1 and one of these co-dependencies exerted synergistic in vitro lethality in AML and post-MPN sAML cells. Co-treatment with LSD1i and the JAKi ruxolitinib was also synergistically lethal against post-MPN sAML cells. LSD1i pre-treatment induced GFI1, PU.1 and CEBPα but depleted c-Myc, overcoming nongenetic resistance to ruxolitinib, or to BETi in post-MPN sAML cells. Co-treatment with LSD1i and BETi or ruxolitinib exerted superior in vivo efficacy against post-MPN sAML cells. These findings highlight LSD1i-based combinations that merit testing for clinical efficacy, especially to overcome nongenetic therapy-resistance in AML and post-MPN sAML.Subject terms: Acute myeloid leukaemia, Targeted therapies 相似文献
49.
Lindy M. Kregting Sylvia Kaljouw Lucie de Jonge Erik E. L. Jansen Elisabeth F. P. Peterse Eveline A. M. Heijnsdijk Nicolien T. van Ravesteyn Iris Lansdorp-Vogelaar Inge M. C. M. de Kok 《British journal of cancer》2021,124(9):1516
Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.Subject terms: Health policy, Population screening, Cancer screening, Cancer screening 相似文献
50.