全文获取类型
收费全文 | 2787篇 |
免费 | 185篇 |
国内免费 | 81篇 |
专业分类
耳鼻咽喉 | 55篇 |
儿科学 | 105篇 |
妇产科学 | 48篇 |
基础医学 | 287篇 |
口腔科学 | 88篇 |
临床医学 | 276篇 |
内科学 | 616篇 |
皮肤病学 | 248篇 |
神经病学 | 142篇 |
特种医学 | 320篇 |
外科学 | 249篇 |
综合类 | 39篇 |
预防医学 | 231篇 |
眼科学 | 38篇 |
药学 | 153篇 |
中国医学 | 10篇 |
肿瘤学 | 148篇 |
出版年
2023年 | 15篇 |
2022年 | 19篇 |
2021年 | 49篇 |
2020年 | 30篇 |
2019年 | 50篇 |
2018年 | 80篇 |
2017年 | 51篇 |
2016年 | 67篇 |
2015年 | 79篇 |
2014年 | 90篇 |
2013年 | 88篇 |
2012年 | 118篇 |
2011年 | 128篇 |
2010年 | 93篇 |
2009年 | 103篇 |
2008年 | 117篇 |
2007年 | 149篇 |
2006年 | 129篇 |
2005年 | 129篇 |
2004年 | 104篇 |
2003年 | 98篇 |
2002年 | 89篇 |
2001年 | 89篇 |
2000年 | 92篇 |
1999年 | 68篇 |
1998年 | 95篇 |
1997年 | 83篇 |
1996年 | 68篇 |
1995年 | 67篇 |
1994年 | 51篇 |
1993年 | 51篇 |
1992年 | 47篇 |
1991年 | 33篇 |
1990年 | 36篇 |
1989年 | 53篇 |
1988年 | 52篇 |
1987年 | 34篇 |
1986年 | 30篇 |
1985年 | 33篇 |
1984年 | 23篇 |
1983年 | 19篇 |
1982年 | 22篇 |
1981年 | 13篇 |
1980年 | 15篇 |
1979年 | 15篇 |
1978年 | 9篇 |
1977年 | 21篇 |
1976年 | 14篇 |
1975年 | 17篇 |
1972年 | 5篇 |
排序方式: 共有3053条查询结果,搜索用时 15 毫秒
31.
Specific allergens enhance elastase release in stimulated neutrophils from asthmatic patients 总被引:12,自引:0,他引:12
Monteseirín J Bonilla I Camacho MJ Chacón P Vega A Chaparro A Conde J Sobrino F 《International archives of allergy and immunology》2003,131(3):174-181
BACKGROUND: The presence of the three forms of IgE receptor - the heterotrimeric high-affinity receptor for IgE (Fc(epsilon)RI), the low-affinity receptor for IgE (Fc(epsilon)RII/CD23) and the Mac-2/IgE-binding protein (epsilonBP) - has been demonstrated on human neutrophils. We have previously shown that specific allergens are able to activate functional responses by neutrophils from allergic patients sensitized to those allergens. Neutrophils are present at the sites of allergic inflammation. The primary (azurophilic) granules of neutrophils contain a variety of enzymes, such as elastase, that might potentiate inflammation. It is not known whether specific allergens are able to elicit elastase release by neutrophils from allergic patients. In addition, we attempted to evaluate the relationship between neutrophil degranulation and lung function of the patients, measured as FEV(1). METHODS: Neutrophils were challenged in vitro with the specific allergens that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Neutrophils from normal subjects were challenged with allergens as control. RESULTS: The in vitro challenge of neutrophils with allergens to which the patients were sensitive elicited a release of elastase by these cells. The in vitro activation of neutrophils was highly allergen specific; allergens other than those accounting for clinical symptoms did not evoke elastase release, and allergens were ineffective on neutrophils from healthy donors. A significant inverse correlation was observed between elastase release and patients' lung function, measured as FEV(1). CONCLUSION: An IgE-dependent mechanism might promote elastase release by neutrophils at allergic sites. There is a significant inverse relationship between levels of elastase released by neutrophils from allergic patients and lung function, as assessed by FEV(1). 相似文献
32.
Montero R Serrano L Dávila V Segura Y Arrieta A Fuentes R Abad I Valencia L Sierra P Camacho R 《Environmental and molecular mutagenesis》2003,42(3):216-222
Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed. 相似文献
33.
Vankeerberghen A; Wei L; Jaspers M; Cassiman JJ; Nilius B; Cuppens H 《Human molecular genetics》1998,7(11):1761-1769
In order to gain a better insight into the structure and function of the
regulatory domain (RD) of the cystic fibrosis transmembrane conductance
regulator (CFTR) protein, 19 RD missense mutations that had been identified
in patients were functionally characterized. Nine of these (I601F, L610S,
A613T, D614G, I618T, L619S, H620P, G628R and L633P) resulted in aberrant
processing. No or a very small number of functional CFTR proteins will
therefore appear at the cell membrane in cells expressing these mutants.
These mutations were clustered in the N- terminal part of the RD,
suggesting that this subdomain has a folding pattern that is very sensitive
to amino acid changes. Mutations that caused no aberrant processing were
further characterized at the electrophysiological level. First, they were
studied at the whole cell level in Xenopus laevis oocytes. Mutants that
induced a whole cell current that was significantly different from
wild-type CFTR were subsequently analysed at the single channel level in
COS1 cells transiently expressing the different mutant and wild-type
proteins. Three mutant chloride channels, G622D, R792G and E822K CFTR, were
characterized by significantly lower intrinsic chloride channel activities
compared with wild-type CFTR. Two mutations, H620Q and A800G, resulted in
increased intrinsic chloride transport activities. Finally, T665S and E826K
CFTR had single channel properties not significantly different from
wild-type CFTR.
相似文献
34.
Monteseirín J Bonilla I Chacón P Vega A Camacho MJ Guardia P Conde J Sobrino F 《Allergy》2003,58(10):1027-1032
BACKGROUND: CD14 is a most important monocyte surface molecule. Recently, it has been reported that there is an important relationship between CD14 and immunoglobulin E, and that regulation of CD14 expression is an effector mechanism mediating apoptosis of monocytes. OBJECTIVE: The present study was designed to determine whether specific allergens were able to modulate CD14 expression and apoptosis by monocytes from allergic patients or whether specific immunotherapy (IT) might affect these processes. METHODS: One group of adult allergic asthmatic patients had received IT for the previous 3 years. Another similar group was not treated with IT. We challenged peripheral blood monocytes from both groups of asthmatic patients in vitro with the specific allergen that produced clinical symptoms in asthmatic patients. The cells were also challenged with allergen to which the patients were not sensitive. Monocytes from normal subjects were also challenged with allergens. Expression of CD14 on the monocyte surface was analyzed by flow cytometry, and soluble CD14 (sCD14) in culture supernatant by enzyme-linked immunosorbent assay. The three groups of subjects were challenged with allergens, and apoptosis was analyzed by flow cytometry. RESULTS: When monocytes from non-IT-treated asthmatic patients were cultivated with the allergens to which the patients were sensitive, a significant up-regulation on the monocyte surface was observed compared with results from the healthy group (P < 0.003) and from the IT asthmatic group (P < 0.003). A significantly higher sCD14 level was observed in the culture supernatant of the monocytes from the IT asthmatic group were observed compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (P < 0.001). A significantly higher apoptosis level was observed in monocytes from the IT asthmatic group compared with those from the healthy group (P < 0.001) and those from the non-IT asthmatic group (<0.001). CONCLUSIONS: We present evidence that the expression of CD14 on the surface of monocytes and the apoptosis of the same cells can be modulated by an allergen-dependent mechanism. These processes can be affected by IT. 相似文献
35.
Oliveira CJ Carvalho LF Fernandes SA Tavechio AT Menezes CC Domingues FJ 《Microbial drug resistance (Larchmont, N.Y.)》2002,8(4):407-411
The aim of this study was to determine the antimicrobial resistance patterns of Salmonella strains isolated from slaughter-age pigs and environmental samples collected at modern swine raising facilities in Brazil. Seventeen isolates of six serotypes of Salmonella enterica subsp. enterica were isolated out of 1,026 collected samples: Salmonella Typhimurium (1), Salmonella Agona (5), Salmonella Sandiego (5), Salmonella Rissen (1), Salmonella Senftenberg (4), and Salmonella Javiana (1). Resistance patterns were determined to extended-spectrum penicillin (ampicillin), broad-spectrum cephalosporins (cefotaxime and ceftriaxone), aminoglycosides (streptomycin, neomycin, gentamicin, amikacin, and tobramycin), narrow-spectrum quinolone (nalidixic acid), broad-spectrum quinolone (ciprofloxacin and norfloxacin), tetracycline, trimethoprim, and chloramphenicol. Antimicrobial resistance patterns varied among serotypes, but isolates from a single serotype consistently showed the same resistance profile. All isolates were resistant to tetracycline, streptomycin, and nalidixic acid. One isolate, Salmonella Rissen, was also resistant to cefotaxime and tobramycin. All serotypes were susceptible to ceftriaxone, norfloxacin, ciprofloxacin, ampicillin, gentamicin, and chloramphenicol. The high resistance to tetracycline and streptomycin may be linked to their common use as therapeutic drugs on the tested farms. No relation was seen between nalidixic acid and fluoroquinolone resistance. 相似文献
36.
37.
Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B) 总被引:4,自引:1,他引:4
Sanfilippo B syndrome is caused by a deficiency of alpha-N-
acetylglucosaminidase, a lysosomal enzyme involved in the degradation of
heparan sulphate. Accumulation of the substrate in lysosomes results in
degeneration of the central nervous system with progressive dementia often
combined with hyperactivity and aggressive behaviour. In order to clone the
deficient gene, we purified the enzyme from human placenta and obtained
amino acid sequence information. Alignment of one of the CNBr generated
internal peptides to sequence from the database revealed the chromosomal
location of the gene in the 5' upstream flanking region of the gene for
17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence
was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and
analyse its gene structure. The gene is fully contained in the 5' upstream
flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and
interrupted by five introns. The cDNA clone has a length of 2575 bp and
encodes a protein of 743 amino acids. Chinese hamster ovary cells
transfected with the cDNA construct show alpha-N-acetylglucosaminidase
activity about 17-fold over background. This will allow correction studies
with NAG deficient Sanfilippo B cell lines and facilitate the development
of enzyme replacement therapy for these patients.
相似文献
38.
Zaeem Lone Prithvi B. Murthy JJ Haijing Zhang Kyle J. Ericson Lewis Thomas Abhinav Khanna Georges-Pascal Haber Byron H. Lee 《Urologic oncology》2021,39(5):301.e1-301.e9
PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m2. Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m2. Renal function decline was defined as a ≥10 ml/min/1.73m2 drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m2, P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline. 相似文献
39.
40.
Espinet B Solé F Pedro C Garcia M Bellosillo B Salido M Florensa L Camacho FI Baró T Lloreta J Serrano S 《Human pathology》2005,36(11):1232-1237
Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions. 相似文献