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61.
62.

Objectives

To investigate lymph node invasion (LNI) rates in prostate cancer (PCa) patients. Recent studies demonstrated an inverse stage migration in PCa patients toward more advanced and unfavorable diseases. We hypothesized that this trend is also evident in LNI rates, in PCa patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND).

Patients and methods

Within the Surveillance, Epidemiology, and End Results database (2004–2014), we identified patients who underwent RP and PLND. Annual trends of LNI rates and PLND extent were plotted. Univariable and multivariable logistic regression models tested the hypothesis that LNI rates are increasing annually, even after adjustment for clinical or pathological characteristics.

Results

Of 96,874 patients treated with RP and PLND, 4.1% (n = 4,002) exhibited LNI. The rate of LNI (2.5%–6.6%.), the mean (6.5–8.4) and median (5–6) number of removed lymph nodes increased during the study period. In multivariable logistic regression models, more contemporary year of diagnosis was associated with higher LNI rate, when year of diagnosis was modeled as a continuous, categorized or cubic spline variable, with adjustment for either clinical (prostate specific antigen, clinical tumor stage, and biopsy Gleason group) or pathological characteristics (pathologic tumor stage and Gleason group), as well as PLND extent (number of removed lymph nodes).

Conclusion

We confirmed the hypothesis about increasing LNI rate over time in RP patients. This observation implies an increasing rate of unfavorable PCa defined as LNI. This finding is novel for contemporary epidemiological North American or European databases.  相似文献   
63.

Background Context

Magnetic resonance imaging (MRI) has the potential to identify pathology contributing to neck pain. However, the importance of findings on MRI remains unclear.

Purpose

We aimed to investigate whether findings on cervical spine MRI predict future neck pain.

Study Design

A systematic review was carried out.

Patient Sample

People with or without neck pain comprised the study sample.

Outcome Measures

Clinically important neck pain outcomes such as pain and disability.

Methods

The review protocol was registered on PROSPERO [CRD42016049228]. MEDLINE, CINAHL, and EMBASE databases were searched. Prospective cohort studies investigating the association between baseline MRI findings and clinical outcome were included. Cohorts with serious underlying diseases as the cause of their neck pain were excluded. Associations between MRI findings and neck pain outcomes were extracted from the included studies.

Results

A total of 12 studies met all inclusion criteria. Eight studies presented data on participants with current neck pain, two studies included a mixed sample, and two studies included a sample of participants with no current neck pain. Because of the heterogeneity between the studies in terms of MRI findings, populations, and clinical outcomes investigated, it was not possible to pool the results. No consistent associations between MRI findings and future outcomes were identified. Single studies of populations with neck pain reported significant associations for neck muscle fatty infiltrate (risk ratio [RR]: 21.00, 95% confidence interval [CI]: 2.97–148.31) with persistent neck disability; disc protrusion (mean difference ranged from ?1.83 to ?2.88 on a 10-point pain scale), and disc degeneration (RR: 0.59; 95% CI: 0.36–0.98) with neck pain. In a population without pain, the development of foraminal stenosis over a 10-year period was associated with development of neck pain (RR: 2.99; 95% CI: 1.23–7.23).

Conclusion

The limited number, heterogeneity, and small sample size of the included studies do not permit definitive conclusions on the association between MRI findings of the cervical spine with future neck pain.  相似文献   
64.
In mammals, the 5’‐methylcytosine (5mC) modification in the genomic DNA contributes to the dynamic control of gene expression. 5mC erasure is required for the activation of developmental programs and occurs either by passive dilution through DNA replication, or by enzymatic oxidation of the methyl mark to 5‐hydroxymethylcytosine (5hmC), which can persist as such or undergo further oxidation and enzymatic removal. The relative contribution of each mechanism to epigenetic control in dynamic biological systems still remains a compelling question. To explore this critical issue, we used primary human T lymphocytes, in which two cellular states can be clearly identified, namely quiescent naïve T cells, which are slowly or rarely proliferating, and rapidly proliferating activated T cells. We found that active mechanisms of methylation removal were selectively at work in naïve T cells, while memory T lymphocytes entirely relied on passive, replication‐dependent dilution, suggesting that proliferative capacity influences the choice of the preferential demethylation mechanism. Active processes of demethylation appear to be critical in quiescent naïve T lymphocytes for the maintenance of regulatory regions poised for rapid responses to physiological stimuli.  相似文献   
65.
CKD is increasingly prevalent in pregnancy. In the Torino-Cagliari Observational Study (TOCOS), we assessed whether the risk for adverse pregnancy outcomes is associated with CKD by comparing pregnancy outcomes of 504 pregnancies in women with CKD to outcomes of 836 low-risk pregnancies in women without CKD. The presence of hypertension, proteinuria (>1 g/d), systemic disease, and CKD stage (at referral) were assessed at baseline. The following outcomes were studied: cesarean section, preterm delivery, and early preterm delivery; small for gestational age (SGA); need for neonatal intensive care unit (NICU); new onset of hypertension; new onset/doubling of proteinuria; CKD stage shift; “general” combined outcome (preterm delivery, NICU, SGA); and “severe” combined outcome (early preterm delivery, NICU, SGA). The risk for adverse outcomes increased across stages (for stage 1 versus stages 4–5: “general” combined outcome, 34.1% versus 90.0%; “severe” combined outcome, 21.4% versus 80.0%; P<0.001). In women with stage 1 CKD, preterm delivery was associated with baseline hypertension (odds ratio [OR], 3.42; 95% confidence interval [95% CI], 1.87 to 6.21), systemic disease (OR, 3.13; 95% CI, 1.51 to 6.50), and proteinuria (OR, 3.69; 95% CI, 1.63 to 8.36). However, stage 1 CKD remained associated with adverse pregnancy outcomes (general combined outcome) in women without baseline hypertension, proteinuria, or systemic disease (OR, 1.88; 95% CI, 1.27 to 2.79). The risk of intrauterine death did not differ between patients and controls. Findings from this prospective study suggest a “baseline risk” for adverse pregnancy-related outcomes linked to CKD.  相似文献   
66.
67.
68.

Introduction

One of the most common sites of distant metastasization of prostate cancer is bone, but to date reliable biomarkers able to predict the risk and timing of bone metastasization are still lacking.

Patients and methods

Surgically resected paraffin embedded samples from 12 primary prostate cancers that developed metachronous bone metastasis at different time points were studied (six cases within 2 years, six cases after 5 years from surgery). A targeted next-generation DNA and RNA sequencing able to assess simultaneously mutations, copy number alterations and fusion events of multiple genes was used. Immunohistochemistry was used to assess mTOR pathway activation.

Results

Rearrangements of ETS family genes, molecular alterations in PTEN and TP53 genes were detected in 10, 6 and 5 cancers, respectively. Nine samples showed TMPRSS2-ERG fusions, which were associated with increased ERG expression at immunohistochemistry. mTOR pathway activation was documented in 6 patients, with a clear trend of prevalence in late-metastatic patients (p?=?0.08).

Conclusions

A simultaneous next-generation targeted DNA and RNA sequencing is applicable on routine formalin-fixed paraffin-embedded tissues to assess the multigene molecular asset of individual prostate cancers. This approach, coupled with immunohistochemistry for ERG and mTOR pathway proteins, may help to better characterize prostate cancer molecular features with a potential impact on clinical decisions.  相似文献   
69.

Objective

Individuals diagnosed with acute HIV infection (AHI) are highly infectious and require immediate HIV prevention efforts to minimize their likelihood of transmitting HIV to others. We sought to explore the relevance of Motivational Interviewing (MI), an evidence-based counseling method, for Malawians with AHI.

Methods

We designed a MI-based intervention called “Uphungu Wanga” to support risk reduction efforts immediately after AHI diagnosis. It was adapted from Options and SafeTalk interventions, and refined through formative research and input from Malawian team members and training participants. We conducted qualitative interviews with counselors and participants to explore the relevance of MI in this context.

Results

Intervention adaptation required careful consideration of Malawian cultural context and the needs of people with AHI. Uphungu Wanga's content was relevant and key MI techniques of topic selection and goal setting were viewed positively by counselors and participants. However, rating levels of importance and confidence did not appear to help participants to explore behavior change as intended.

Conclusion

Uphungu Wanga may have provided some added benefits beyond “brief education” standard of care counseling for Malawians with AHI.

Practice implications

MI techniques of topic selection and goal setting may enhance prevention education and counseling for Malawians with AHI.  相似文献   
70.
The optimal viral load threshold at which to initiate preemptive cytomegalovirus (CMV) therapy in hematopoietic cell transplantation (HCT) recipients remains to be defined. In an effort to address this question, we conducted a retrospective study of 174 allogeneic HCT recipients who underwent transplantation at a single center between August 2012 and April 2016. During this period, preemptive therapy was initiated at the discretion of the treating clinician. A total of 109 patients (63%) developed CMV viremia. The median time to reactivation was 17 days (interquartile range, IQR, 7-30 days) post-HCT. A peak viremia ≥150?IU/mL was strongly associated with a reduced probability of spontaneous clearance (relative risk, .16; 95% confidence interval, .1-.27), independent of established clinical risk factors, including CMV donor serostatus, exposure to antithymocyte globulin, and underlying lymphoid malignancy. The median time to clearance of viremia was significantly shorter in those who started therapy at CMV <350?IU/mL (19 days; IQR, 11-35 days) compared with those who started antiviral therapy at higher viremia thresholds (33 days; IQR, 21-42 days; P?=?.02). The occurrence of treatment-associated cytopenias was frequent but similar in patients who started preemptive therapy at CMV <350?IU/mL and those who started at CMV >350?IU/mL (44% versus 57%; P?=?.42). Unresolved CMV viremia by treatment day 35 was associated with increased risk of therapeutic failure (32% versus 0%; P?=?.001). Achieving eradication of CMV viremia by treatment day 35 was associated with a 74% reduction in 1-year nonrelapse mortality (NRM) (adjusted hazard ratio [HR], .26; 95% confidence interval [CI], .1-.8; P?=?.02), whereas therapeutic failure was associated with a significant increase in the probability of 1-year NRM (adjusted HR, 26; 95% CI, 8-87; P?<.0001). We conclude that among allogeneic HCT patients, a peak CMV viremia ≥150?IU/mL is associated with a >80% reduction in the probability of spontaneous clearance independent of ATG administration, CMV donor serostatus, and lymphoid malignancy, and is a reasonable cutoff for preemptive therapy. Delaying initiation of therapy until a CMV value ≥350?IU/mL is associated with more protracted CMV viremia, and unresolved viremia by treatment day 35 is associated with a significant increase in NRM.  相似文献   
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