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101.

Background

Limited data are available regarding the incidence, survival patterns, and long-term outcomes of natural killer (NK)/T-cell neoplasms in the United States.

Patients and Methods

We performed a retrospective study of patients with NK/T-cell neoplasms diagnosed from 2001 to 2014 using the Surveillance, Epidemiology, and End Results program database. The Kaplan-Meier method was used to estimate the overall survival difference among the subgroups. Multivariate analyses were used to determine the factors affecting survival.

Results

For the 797 patients with NK/T-cell lymphoma, nasal type, the median age at diagnosis was 53 years, and males tended to be younger at diagnosis (P < .0001). The incidence of the disease increased from 0.4 in 2001 to 0.8 in 2014 per 1,000,000 individuals. The incidence was significantly greater in Hispanic patients compared with that in non-Hispanic patients (rate ratio, 3.03; P = .0001). The median overall survival was 20 months (range, 2-73 months) and varied significantly according to the primary site (P < .0001) and the disease stage at diagnosis (P < .0001). NK/T-cell lymphoma patients had an increased risk of acute myeloid leukemia (standardized incidence ratio, 18.77; 95% confidence interval, 2.27-67.81). For the 105 NK/T-cell leukemia patients, the median age at diagnosis was 58 years (range, 4-95 years). The overall incidence of the disease was 0.09 per 1,000,000 individuals and was significantly greater in males (rate ratio, 0.41; P < .0001). Unlike NK/T-cell lymphoma, no racial disparities were found in the incidence. The median overall survival was 17 months (range, 0-36 months).

Conclusion

The incidence of NK/T-cell lymphoma, nasal type, in the United States has at least doubled in the past decade, with the greatest predilection among Hispanics. Patients with NK/T-cell lymphoma might have an increased risk of the subsequent development of acute myeloid leukemia.  相似文献   
102.

Background

Activation of the JAK/STAT pathway is common in triple-negative breast cancer (TNBC) and affects the expression of genes controlling immune signaling. A subset of TNBC cases will have somatic amplification of chromosome 9p24.1, encoding PD-L1, PD-L2, and JAK2, which has been associated with decreased survival.

Materials and Methods

Eleven TNBC cell lines were evaluated using array comparative genomic hybridization. A copy number gain was defined as an array comparative genomic hybridization log2 ratio of ≥ 1. Cell surface expression of programmed cell death ligand 1 (PD-L1) was detected using flow cytometry and compared with the median fluorescence intensity of isotype control immunoglobulin. To selectively inhibit JAK2, lentiviral vectors encoding 2 different short hairpin RNA (shRNA) were generated. JAK2, STAT1, STAT3, phosphorylated (p) STAT1, and pSTAT3 expression were measured by immunoblot. Statistical significance was defined as P < .05.

Results

The cell line HCC70 had 9p24.1 copy number amplification that was associated with both increased JAK2 and pSTAT3; however, knockdown of JAK2 inhibited cell growth independently of 9p24.1 copy number status. In TNBC cell lines with 9p24.1 gain or amplification, PD-L1 expression rapidly and strikingly increased 5- to 38-fold with interferon-γ (P < .05), and inducible PD-L1 expression was completely blocked by JAK2 knockdown and the JAK1/2 inhibitor ruxolitinib. In tumor tissue, expression of interferon-γ–related genes correlated with 9p24.1 copy number status.

Conclusion

These data suggest that the JAK2/STAT1 pathway in TNBC might regulate the dynamic expression of PD-L1 that is induced in the setting of an inflammatory response. Inhibition of JAK2 might provide a synergistic therapy when combined with other immunotherapies in the subset of TNBC with 9p24.1 amplification.  相似文献   
103.
Abstract

Musculoskeletal infections caused by bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa in children and adults can lead to adverse outcomes including a need for extensive surgical debridement and limb amputation. To enable targeted antimicrobial release in infected tissues, the objective of this study was to design and investigate novel elastin-like polypeptide (ELP)-based thermally sensitive liposomes in vitro. ELP biopolymers can change their phase behaviour at higher temperatures. We hypothesised that ELP-TSL will improve therapeutic efficacy by releasing antimicrobial payloads locally at higher temperatures (≥39?°C). ELP-TSL library were formulated by varying cholesterol and phospholipid composition by the thin film and extrusion method. A broad-spectrum antimicrobial (Ciprofloxacin or Cipro) was encapsulated inside the liposomes by the ammonium sulphate gradient method. Cipro release from ELP-TSLs was assessed in physiological buffers containing ~25% serum by fluorescence spectroscopy, and efficacy against Staphylococcus aureus and Pseudomonas aeruginosa was assessed by disc diffusion and planktonic assay. Active loading of Cipro achieved an encapsulation efficiency of 40–70% in the ELP-TSL depending upon composition. ELP-TSL Cipro release was near complete at ≥39?°C; however, the release rates could be delayed by cholesterol. Triggered release of Cipro from ELP-TSL at ~42?°C induced significant killing of S. aureus and P. aeruginosa compared to 37?°C. Our in vitro data suggest that ELP-TSL may potentially improve bacterial wound therapy in patients.  相似文献   
104.

Objective

To identify areas of deficiencies and gaps in child protection services in Northern Sri Lanka. Also, to help in recommending strategies, programmes of interventions for addressing issues of child abuse and advice the legal system.

Methods

A retrospective study was done to determine the socio-demographic details, type of abuse, clinical profile, relationship of the perpetrator and nature of abuse among children admitted to a tertiary care centre from 2009 through 2014, a period after cessation of a 60-y conflict. Data were obtained from hospital based records and records maintained at the district probation office.

Results

Seven hundred twenty cases were referred to the tertiary care centre with abuse. Majority of the children were from the Jaffna district, the northern city of the war affected area and mean age of the children affected was 14.5 ± 2.6 y. Females were affected more than the males and 352 children were seen following sexual abuse. The clinical examination showed penetrative injury in 15 %. The perpetrator was known in 70 % of the situations and the victim was coerced into a relationship for abuse. Attempted suicide was seen in significant numbers during the immediate post war period and school dropout and delinquent behaviour was seen in later years.

Conclusions

The problem of child abuse is considerable in this region and there is an urgent need to strengthen the services offered to the victims. Urgent steps are needed to safeguard these children, especially in the war affected areas.
  相似文献   
105.
Carbamazepine (CBZ) is a BCS Class II drug with poor solubility profile. In order to improve the physicochemical properties of CBZ, albumin (HSA)-bound CBZ nanoparticles (ABCns) were prepared. Drug-loading studies indicated that monomeric ABCns can be fabricated by self-assembly of anhydrous form III of CBZ and HSA in molar ratios of 1:1 or 2:1 within 0.5?h in phosphate buffer pH 7.4 with particle size in the range of 10–20?nm. Approximately 73–76% of the CBZ was encapsulated within HSA and 20–40% CBZ was released from the ABCns over 8 days. In conclusion, novel ABCns can be fabricated with sustained-release of CBZ for over 8 days which can significantly improve the physicochemical profile of CBZ.  相似文献   
106.
Imprint cytology of the gastric mucosa has been found to be very simple, inexpensive, and rapid for diagnosing Helicobacter pylori infection. However, there is a fear that preparing imprint smears may damage the biopsy specimen for subsequent histologic examination. This study was planned to investigate whether this damage happens. Four antral biopsy specimens were obtained from each of the 100 patients undergoing upper gastrointestinal endoscopy. Imprint smears were made from two biopsy specimens, which were then fixed in 10% formal saline and sent for histologic study. The third and fourth biopsy specimens were directly fixed in 10% formal saline for histologic examination. Two pathologists examined the imprint smears. Agreement between the two observers was observed in 97% of cases. Beyond-chance agreement was good with a kappa index of 0.90. H. pylori organisms were seen in 82% of biopsy specimens from which imprint smears were prepared and in the same percentage of biopsy specimens that were processed directly. The pathologists could not identify the histologic sections from which imprints were made. It is concluded that imprint cytology is an excellent method of diagnosing H. pylori infection and that preparing imprint smears does not alter the quality of the tissue. The same biopsy specimen can be used for histologic studies. Diagn. Cytopathol. 1998;18:330–332. © 1998 Wiley-Liss, Inc.  相似文献   
107.
108.
109.
Both iron deficiency anaemia and dyslipidaemia are widely prevalent public health problems, especially in the Indian population. Some link has been suggested between the two potentially morbid conditions but a sufficient Indian study could not be found in this regard. This study was planned to find the changes in serum lipid profile in adult Indian patients with iron deficiency anaemia and the effect of oral iron therapy on them. Seventy patients with iron deficiency anaemia and 70 age and sex matched healthy controls, in the age group of 18-35 years were investigated for any possible changes in serum lipid profile ie, triglycerides, total cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol and low density lipoprotein cholesterol. The patients were followed up after 3 months of oral iron therapy. The results are shown as mean +/- standard deviation. Triglycerides and very low density lipoprotein cholesterol levels were found to be significantly (p < 0.001) elevated in the iron deficiency anaemia group (151.87 +/- 48.06 mg/dl and 30.40 +/- 9.71 mg/dl) as compared to controls (109.99 +/- 30.81 mg/dl and 21.96 +/- 6.69 mg/dl), whereas levels of low density lipoprotein cholesterol were found to be significantly (p = 0.02) lower in patients (90.96 +/- 41.55 mg/dl) as compared to controls (105.24 +/- 26.45 mg/dl). However, after treatment (in 43 patients) there was significant (p < 0.001) reduction in the levels of triglycerides and very low density lipoprotein cholesterol (111.56 +/- 26.87 mg/dl and 22.30 +/- 5.36 mg/dl) when compared to their pretreatment levels (154.70 +/- 53.89 mg/dl and 30.93 +/- 10.84 mg/dl), whereas low density lipoprotein cholesterol levels did not show any significant change. These findings indicate that iron deficiency anaemia in Indian adults is attended by abnormal serum lipid profile, which responds significantly to iron therapy.  相似文献   
110.
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