全文获取类型
收费全文 | 5258篇 |
免费 | 270篇 |
国内免费 | 22篇 |
专业分类
耳鼻咽喉 | 53篇 |
儿科学 | 398篇 |
妇产科学 | 87篇 |
基础医学 | 431篇 |
口腔科学 | 133篇 |
临床医学 | 365篇 |
内科学 | 1031篇 |
皮肤病学 | 57篇 |
神经病学 | 390篇 |
特种医学 | 134篇 |
外科学 | 1128篇 |
综合类 | 128篇 |
现状与发展 | 1篇 |
一般理论 | 3篇 |
预防医学 | 226篇 |
眼科学 | 163篇 |
药学 | 392篇 |
中国医学 | 15篇 |
肿瘤学 | 415篇 |
出版年
2023年 | 47篇 |
2022年 | 113篇 |
2021年 | 243篇 |
2020年 | 110篇 |
2019年 | 154篇 |
2018年 | 210篇 |
2017年 | 140篇 |
2016年 | 174篇 |
2015年 | 180篇 |
2014年 | 238篇 |
2013年 | 292篇 |
2012年 | 438篇 |
2011年 | 468篇 |
2010年 | 256篇 |
2009年 | 224篇 |
2008年 | 306篇 |
2007年 | 315篇 |
2006年 | 259篇 |
2005年 | 230篇 |
2004年 | 201篇 |
2003年 | 162篇 |
2002年 | 119篇 |
2001年 | 59篇 |
2000年 | 54篇 |
1999年 | 50篇 |
1998年 | 29篇 |
1997年 | 23篇 |
1996年 | 15篇 |
1995年 | 14篇 |
1992年 | 31篇 |
1991年 | 32篇 |
1990年 | 24篇 |
1989年 | 18篇 |
1988年 | 28篇 |
1987年 | 16篇 |
1986年 | 13篇 |
1985年 | 17篇 |
1984年 | 12篇 |
1983年 | 16篇 |
1982年 | 14篇 |
1981年 | 10篇 |
1979年 | 10篇 |
1978年 | 19篇 |
1977年 | 21篇 |
1976年 | 12篇 |
1975年 | 11篇 |
1974年 | 20篇 |
1973年 | 14篇 |
1972年 | 15篇 |
1970年 | 12篇 |
排序方式: 共有5550条查询结果,搜索用时 0 毫秒
31.
Altered matrix degradation may be playing a role in the development of initial mesangial expansion and subsequent glomerulosclerosis in persons with heroin abuse. We studied whether morphine, a metabolite of heroin, had any effect on lysosomal content of cathepsin B and L in mesangial cells. Morphine (10–6 M) increased (P<0.01) mesangial cathepsin B and L activity (control, 22.1+2.2 vs. morphine, 31.4+1.4 mol NMec/g protein,N=5). Morphine (10–6 M) also increased (P<0.01) glomerular cathepsin B and L activity (control, 0.1+0.01 vs. morphine, 2.2±0.2 pmol NMec/g protein,N=3). This effect of morphine occurred in a dose-dependent manner. These results suggest that morphine enhances cathepsin B and L activity in mesangial cells and isolated glomeruli. This effect of morphine may enhance capacity of mesangial cells to degrade increased amount of mesangial macromolecules. 相似文献
32.
Awasthi S Singhal SS Pandya U Gopal S Zimniak P Singh SV Awasthi YC 《Toxicology and applied pharmacology》1999,155(3):215-226
We have recently demonstrated mutually inhibitory ATP-dependent transport of dinitrophenyl-S-glutathione (DNP-SG) and doxorubicin by DNP-SG ATPase purified from human erythrocyte membranes (S. Awasthi et al., 1998a,b). Our previous studies indicate a broad substrate specificity for this transport mechanism, including some P-glycoprotein substrates. Present studies were carried out to determine whether colchicine (COL), a classical P-glycoprotein substrate, could be transported by purified human erythrocyte DNP-SG ATPase reconstituted in artificial liposomes. We also investigated whether leukotriene C4 (LTC4), an endogenous proinflammatory glutathione-conjugate derived from arachidonic acid, would inhibit colchicine transport. Uptake of COL was compared in proteoliposomes reconstituted with the purified DNP-SG ATPase as well as control liposomes in the presence or absence of ATP. Increased colchicine uptake was observed upon addition of ATP to proteoliposomes, but not control liposomes. Uptake was linear with respect to the amount of vesicle protein used. Sensitivity to osmolarity was consistent with intravesicular COL accumulation. The ATP-dependent colchicine uptake was sensitive to temperature in a manner consistent with a protein-mediated transport process with activation energy of 7.3 kcal/mol. Time-dependent COL uptake by proteoliposomes in the presence of ATP was consistent with a single compartment model with an apparent rate constant of 0.21 +/- 0.02 min-1. Kinetic studies indicated a saturable behavior with respect to ATP (Km 2.3 +/- 0.7 mM) and colchicine (Km 4.3 +/- 0.2 microM). LTC4 was found to be a competitive inhibitor of COL transport (Kis 16.4 microM). Since DNP-SG ATPase is present in many tissues, it may play an important role in determining colchicine accumulation in cells. Increased LTC4 would tend to increase cellular COL accumulation. 相似文献
33.
R. B. Rastogi R. L. Singhal Y. D. Lapierre 《Journal of neural transmission (Vienna, Austria : 1996)》1981,50(2-4):139-148
Summary The effect of chronic apomorphine treatment on behavioural activity as well as brain dopamine metabolism was studied in normal and neonatally L-triiodothyronine-treated rats. Neonatal hyperthyroidism was accompanied by an increase in spontaneous locomotor activity as well as by enhanced synthesis and release of dopamine as evidenced by increased catecholamine synthesis in crude synaptosomal preparation (P2 pellet), elevated tyrosine hydroxylase activity and higher concentrations of homovanillic acid and 3, 4-dihydroxyphenylacetic acid in striatum of rats. Repeated apomorphine treatment (1 mg/kg/day s.c.) for 15 days, beginning from the 15th day of age, produced hypermobility and stereotyped behaviour (consisting of sniffing, gnawing, rearing) which appeared to be more pronounced in neonatally hyperthyroid rats than in normal controls. In addition, apomorphine-treated hyperthyroid animals marched in a row with straub tail, and displayed increased aggressiveness and bizarre social behaviour consisting of mock fighting when left in pairs. In contrast to normal rats, apomorphine-treated hyperthyroid animals displayed marked hyperactivity which was evident even at 24 hours after the last injection of apomorphine. Administration of apomorphine resulted in significant decreases in striatal tyrosine hydroxylase, catecholamine synthesis in crude synaptosomal preparation (P2 pellet) as well as dopamine metabolite levels in brains of both normal and hyperthyroid animals. Our present data showing that apomorphine potentiates behavioural activity in hyperthyroid rats suggest that L-triiodothyronine and apomorphine probably share certain features common to activating dopaminergic neurons in the brain. 相似文献
34.
Sanjiv Sharma S. C. Sharma Sandeep Singhal Y. N. Mehra B. D. Gupta Sushmita Ghoshal A. P. S. Sandhu 《Indian journal of otolaryngology and head and neck surgery》1991,43(4):191-194
A retrospective analysis was performed of 250 cases of carcinoma of the maxillary antrum seen over a 10 years period (1975–1984). 98.24% patients were seen in T3 and T4 stages (UICC 1985). 40.7% patients presented with clinically palpable nodes. 42.9% patients were treated by radical radiation and 18.6% by a combination of preoperative radiation followed by surgery. Rest 38.5% patients were treated with palliative intention. Three year disease free survival was 39.58% with radiation alone and 51.91% with combined modality treatment which includes patients salvaged by surgery. Failures were mainly at the local site, 75.86% with radiation alone and 60% with combined modality treatment. Combined modality treatment, preferably preoperative radiation followed by radical surgery, gives the best results in the management of carcinoma of the maxillary antrum. 相似文献
35.
Terry Y Shibuya Sanghun Kim Kevin Nguyen Johnny Do Christine E McLaren Kuo-Tung Li Wen-Pin Chen Parag Parikh Ashish Wadhwa Xiaolin Zi Vincent Y Chen Hau-Sin Wong William B Armstrong George H Yoo 《Clinical cancer research》2004,10(20):7088-7099
PURPOSE: We have proposed to characterize the mechanism through which bioactive surgical sutures generate a T(H)1 immune response and to define the immune-stimulating half-life of the sutures. EXPERIMENTAL DESIGN: Bioactive sutures of interferon gamma (IFNgamma), interleukin 2 (IL-2), anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma sutures were used to stimulate lymphocytes from normal donors and from head and neck cancer patients in vitro over a 24-day period. Cell supernatants were analyzed by ELISA, and T cells were phenotyped to characterize the immune response generated. Intracellular cytokine staining was performed to measure the expansion of flu-specific T cells. Electromobility shift assay and supershift assay were used to measure the intranuclear DNA binding activity of nuclear factor kappaB and its p65 subunit in T cells activated by sutures in the presence and absence of a proteasome inhibitor, MG-132. RESULTS: Anti-CD3/CD28, anti-CD3/CD28 + IL-2, or anti-CD3/CD28 + IFNgamma generated a prolonged T(H)1 immune response for 18 days in vitro. Anti-CD3/CD28 expanded flu-specific T cells. Activated T cells demonstrated enhanced CD40 ligand (CD40L) expression within 72 hours of stimulation, which stimulated other cells to secrete IL-12. Stimulated T cells demonstrated increased intranuclear expression of nuclear factor-kappaB, which was blocked by MG-132, and also reduced CD40L and IL-12 expression. CONCLUSIONS: This is the first report to demonstrate that bioactive surgical sutures can generate a prolonged T(H)1 immune response and expand flu-specific T cells. Bioactive sutures, which are primarily a T-cell stimulant, also stimulated other cells to secrete IL-12 and prolonged the immune response. Sutures may provide a novel in situ stimulating strategy for enhancing the immune system of cancer patients. 相似文献
36.
RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. 总被引:21,自引:0,他引:21
Gerold Bepler Swati Sharma Alan Cantor Ashish Gautam Eric Haura George Simon Anupama Sharma Eric Sommers Lary Robinson 《Journal of clinical oncology》2004,22(10):1878-1885
PURPOSE: RRM1 has important functions in the determination of the malignant phenotype. It controls cell proliferation through deoxynucleotide production and metastatic propensity through PTEN induction. It is located in a region of loss of heterozygosity in non-small-cell lung cancer (NSCLC), which is a predictor of poor survival. We hypothesized that RRM1 expression would be a significant predictor of outcome in NSCLC. PATIENTS AND METHODS: A retrospective data set of 49 patients and a prospective data set of 77 patients with resectable NSCLC were studied. RNA was extracted from tumor and normal lung tissue, and expression of the genes RRM1, PTEN, and RRM2 was determined by real-time quantitative polymerase chain reaction. RESULTS: RRM1 expression was significantly correlated with PTEN and RRM2 expression in tumor tissue. RRM1 and PTEN expression in tumor tissue was highly predictive of overall (P =.011 and.018, respectively) and disease-free survival (P =.002 and.026, respectively). Patients with high levels of expression lived longer and had disease recurrence later than patients with low levels of RRM1 and PTEN. In a multivariate analysis, high RRM1 expression was predictive of long survival independent of tumor stage, performance status, and weight loss. CONCLUSION: RRM1 is a biologically and clinically important determinant of malignant behavior in NSCLC. Knowing the level of expression of this gene adds significant information to management decisions independent of the currently used outcome predictors of tumor stage, performance status, and weight loss. Future clinical trials should stratify patients based on expression of this gene to avoid unwanted biases. 相似文献
37.
Surinder K. Singhal Naresh K. Panda S. B. S. Mann Ashim Dass 《Indian journal of otolaryngology and head and neck surgery》1997,49(3):265-268
Basaloid squamous cell carcinoma is a rare variant of squamous cell carcinoma, Larynx has been an uncommon site of this tumour
which is said to have aggressive biological behaviour with high incidence of cervical and distant metastasis along with second
primary. Two cases of laryngeal basaloid squamous cell carcinoma are reported with relevant review of literature. The submucosal
spread of tumour is highlighted alongwith role of preoperative radio therapy. 相似文献
38.
Background. Klippel-Feil syndrome (KFS) is characterised by congenital vertebral fusion of the cervical spine and a wide spectrum of
associated anomalies. KFS has often been considered a sporadic syndrome. However, since the publication of the original KFS
classification early this century, a number of KFS families have indicated heterogeneity complicated by a broad range of variable
expression. Objective. The two major objectives of this study were (1) to identify differences and similarities in the postnatal appearance, morphology,
position and inheritance of vertebral fusions within and between KFS families and (2) to establish a new KFS classification
focussed on KFS aetiology. Materials and methods. Vertebral fusions were assessed via spinal radiography. Chromosomal karyotypes were performed using routine cytogenetics.
Results. The medical histories of three KFS families are presented. The postnatal time, position and appearance of vertebral fusions,
associated anomalies and mode of inheritance were different for the three KFS families. Four classes of KFS are described
in a comprehensive classification table that allays much of the uncertainty arising from KFS heterogeneity and variable expression.
Conclusion. We have described four different KFS classes (KF1–4) within a comprehensive classification that addresses KFS genetic heterogeneity.
The position of vertebral fusions in the cervical spine and their incidence within affected families are delineating features
of KFS.
Received: 10 October 1997 Accepted: 20 April 1998 相似文献
39.
Sham L. Singla Yogender Singh Kadian Naveen Malhotra Ashish Goyal 《Indian journal of otolaryngology and head and neck surgery》2004,56(2):131-132
Neurilemmoma of the cervical sympathetic chain is a rare nerve tumour. Less than 40 confirmed cases have been reported in
the literature.1 2 Sometimes they can he mistaken as carotid body tumour but usual presentation of these lesions is an asymptomatic
neck mass. Because of the rarity of the tumour we report another case of neurilemmoma arising from cervical sympathetic chain
in a 19 years old male. 相似文献
40.