全文获取类型
收费全文 | 21663篇 |
免费 | 1084篇 |
国内免费 | 118篇 |
专业分类
耳鼻咽喉 | 220篇 |
儿科学 | 387篇 |
妇产科学 | 459篇 |
基础医学 | 2728篇 |
口腔科学 | 1029篇 |
临床医学 | 1566篇 |
内科学 | 5823篇 |
皮肤病学 | 601篇 |
神经病学 | 1732篇 |
特种医学 | 379篇 |
外科学 | 3241篇 |
综合类 | 111篇 |
一般理论 | 4篇 |
预防医学 | 1765篇 |
眼科学 | 438篇 |
药学 | 1262篇 |
中国医学 | 100篇 |
肿瘤学 | 1020篇 |
出版年
2024年 | 13篇 |
2023年 | 158篇 |
2022年 | 371篇 |
2021年 | 811篇 |
2020年 | 441篇 |
2019年 | 699篇 |
2018年 | 859篇 |
2017年 | 503篇 |
2016年 | 471篇 |
2015年 | 664篇 |
2014年 | 942篇 |
2013年 | 1122篇 |
2012年 | 1743篇 |
2011年 | 1887篇 |
2010年 | 985篇 |
2009年 | 926篇 |
2008年 | 1417篇 |
2007年 | 1514篇 |
2006年 | 1416篇 |
2005年 | 1290篇 |
2004年 | 1137篇 |
2003年 | 977篇 |
2002年 | 958篇 |
2001年 | 112篇 |
2000年 | 105篇 |
1999年 | 109篇 |
1998年 | 159篇 |
1997年 | 149篇 |
1996年 | 108篇 |
1995年 | 83篇 |
1994年 | 69篇 |
1993年 | 78篇 |
1992年 | 50篇 |
1991年 | 52篇 |
1990年 | 45篇 |
1989年 | 26篇 |
1988年 | 18篇 |
1987年 | 16篇 |
1986年 | 29篇 |
1985年 | 29篇 |
1984年 | 31篇 |
1983年 | 25篇 |
1982年 | 34篇 |
1981年 | 41篇 |
1980年 | 18篇 |
1979年 | 22篇 |
1978年 | 14篇 |
1976年 | 12篇 |
1974年 | 15篇 |
1971年 | 11篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
91.
Elkins MK Vittinghoff E Baranzini SE Hecht FM Sriram U Busch MP Levy JA Oksenberg JR;San Francisco Primary Infection Group 《Genes and immunity》2005,6(1):66-69
In chronically HIV infected individuals, a number of functional B cell abnormalities have been described. However, the immediate changes that occur in the B cell compartment following viral exposure and how they affect the long-term course of infection are not well understood. We report the longitudinal analysis of B cell repertoires during early infection in untreated and treated individuals receiving highly active antiretroviral therapy (HAART). Analysis was based on IgG heavy chain gene utilization and CDR3 length measurement and relationship with CD4/CD8 counts, viral load, and total serum IgG, and anti-HIV antibodies levels. Repertoires were assessed at baseline and at weeks 2, 4, 12, 24, and 72 after initiation of therapy. The findings indicate a stable peripheral B cell repertoire during the first 72 weeks following infection, particularly in the HAART treated patients. A modest association between B cell repertoire integrity and viremia levels as well as treatment was detected. 相似文献
92.
Inhibition of poly(ADP-ribose) polymerase attenuates the severity of acute pancreatitis and associated lung injury 总被引:4,自引:0,他引:4
Mota RA Sánchez-Bueno F Saenz L Hernández-Espinosa D Jimeno J Tornel PL Martínez-Torrano A Ramírez P Parrilla P Yélamos J 《Laboratory investigation; a journal of technical methods and pathology》2005,85(10):1250-1262
The severity of acute pancreatitis results from the transmigration and activation of leukocytes within the pancreas and the local synthesis and release of proinflammatory-soluble mediators that transform a local injury into a systemic inflammatory response. Poly(ADP-ribose)polymerase-1 (PARP-1) is a nuclear DNA-binding protein that has been shown to play a relevant role in cell necrosis and organ failure in various diseases associated with inflammation. Therefore, we set out to investigate whether the genetic deletion of PARP-1 or PARP-2 (a new member of the PARP family) genes, or pharmacological inhibition of PARP activity might affect the development and severity of acute pancreatitis and pancreatitis-associated lung injury. Secretagogue-induced acute pancreatitis was achieved by 12 hourly intraperitoneal injections of cerulein in mice deficient in PARP-1 or PARP-2 genes, and wild-type (WT) littermate mice untreated or treated with PARP activity inhibitors. The severity of pancreatitis was assessed by measurements of serum amylase, lipase, interleukin-1beta and IL-6, pancreatic water content, histologic grading and pancreas myeloperoxidase (MPO) activity. Lung injury was evaluated by quantifying MPO activity and morphological changes. We found that the severity of acute pancreatitis and pancreatitis-associated lung injury was significantly attenuated in mice lacking PARP-1, but not PARP-2, compared with WT mice. Interestingly, administration of PARP inhibitors, 3-aminobenzamide or PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethyacetamide HCl), in WT mice markedly decreased acute pancreatitis severity and pulmonary-associated injury in a larger extension than genetic deletion of PARP-1. Our results support the potential therapeutic application of PARP inhibitors in the development and severity of acute pancreatitis and associated lung injury. 相似文献
93.
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
94.
Ines Santisteban Francisco X. Arredondo-Vega Susan Kelly Marianne Debre Alain Fischer Jean Louis Prignon Bettina Hilman Jane Eldahr David H. Dreyfus Erwin W. Gelfand P. Lynne Howell Michael S. Hershfield 《Human mutation》1995,5(3):243-250
Three new missense mutations (H15D, A83D, and A179D) and a new splicing defect (573 + 1G→A) in the 5′ splice site of intron 5 were among six mutant adenosine deaminase (ADA) alleles found in three unrelated patients with severe combined immunodeficiency disease, the most common phenotype associated with ADA deficiency. When expressed in vitro, the H15D, A83D, and A179D proteins lacked detectable ADA activity. The splicing defect caused skipping of exon 5, resulting in premature termination of translation and a reduced level of mRNA. H15D is the first naturally occurring mutation of a residue that coordinates directly with the enzyme-associated zinc ion. Molecular modeling based on the atomic coordinates of murine ADA suggests that the D15 mutation would create a cavity or gap between the zinc ion and the side chain carboxylate of D15. This could alter the ability of zinc to activate a water molecule postulated to play a role in the catalytic mechanism. A83 and A179 are not directly involved in the active site, but are conserved residues located respectively in a helix 4 and β strand 4 of the α/β barrel. Replacement of these small hydrophobic Ala residues with the charged, more bulky Asp side chain may distort ADA structure and affect enzyme stability or folding.© 1995 wiley-Liss, Inc. 相似文献
95.
Myxoid leiomyosarcoma of the ovary: Analysis of three cases 总被引:2,自引:0,他引:2
Francisco F. Nogales MD Alberto Ayala MD Isabel Ruiz-Avila MD Juan J. Sirvent MD 《Human pathology》1991,22(12):1268-1273
The first three cases of myxoid leiomyosarcoma occurring in the ovary are reported. Two cases in stage III were found in postmenopausal patients and a further case was found in stage I in a 32-year-old. All masses were large and gelatinous with cystic change, necrosis, and hemorrhage, but both uteri and ligaments and contralateral adnexa appeared normal. Microscopically, the tumors showed a predominantly reticular meshwork of elongated cells surrounded by abundant basophilic material. While electron microscopy proved inconclusive due to nondifferentiation, the use of monoclonal antibodies against smooth muscle actin demonstrated a smooth muscle type of differentiation. The differential diagnosis of this rare ovarian condition includes other myxoid ovarian lesions, such as ovarian edema, myxoma, endodermal sinus tumors, and the sarcomatous component of malignant mixed müllerian tumor and carcinosarcoma, as well as lymphovascular tumors. Since mitotic count due to decreased cellular density is unusually low in myxoid leiomyosarcoma, capsular rupture and clinical stage seem to be more reliable prognostic markers. The highly aggressive behavior of myxoid leiomyosarcoma parallels that of typical ovarian leiomyosarcoma. Two of the three patients in this series died of tumor at 13 and 24 months after diagnosis; the other patient is free of disease at 3 years after diagnosis. 相似文献
96.
Cell cycle “checkpoints” help to ensure the integrity of normal cellular functions prior to replicative DNA synthesis and/or
cell division. Cell kinetic abnormalities, particularly arrests at the G1/S and G2/M cell cycle checkpoints, are induced following
exposure to ionizing radiationin vitro. Following irradiation, cellular signaling pathways may lead to G1 arrest and/or apoptosis at the G1/S cell cycle transition
point. Transfection of cyclin D1, a G1/S cyclin, into a rat embryo cells (REC) results in cellular populations that overexpress
cyclin D1, are transformed morphologically, demonstrate an increased incidence of apoptosis, and are tumorigenic in immune-deficient
mice. Despite such phenotypic changes, transfected cell populations maintain the itegrity of the G1 checkpoint following ionizing
radiation. The transfected cells overexpressing Cyclin D1 have a statistically significant increase in the incidence of apoptosis
as compared to parental REC strains or mock-transfected REC. The work provides further evidence of Cyclin D1 playing a critical
role in maintaining the integrity of the G1/S checkpoint, via the activation of apoptotic pathways following exposure to ionizing
radiationin vitro. 相似文献
97.
The present paper studies a marker of oxidative stress such as heme oxygenase-1 (HO-1), the main heat shock protein. HO-1 expression was induced in the focal region of the cerebellum following experimental subarachnoid hemorrhage (SAH). Lysed blood was injected into the subarachnoid space or cisterna magna region of adult rats. The experimental groups used were: (1) animals injected with lysed blood alone; (2) animals injected with saline alone; (3) lysed blood plus melatonin (10 mg/kg body weight(BW)); (4) lysed blood plus melatonin (10 mg/kg BW injected 1 h before SAH); (5) lysed blood plus melatonin (5 mg/kg BW injected 1 h before SAH); (6) lysed blood plus vitamin E (Trolox; 30 mg/kg BW injected simultaneously); (7) lysed blood plus vitamin E (30 mg/kg BW injected 1 h before SAH); and (8) lysed blood plus vitamin E (15 mg/kg BW injected 1 h before SAH). Animals were sacrificed 24 h later. Injection of lysed blood induced an overexpression of HO-1. Both, melatonin and vitamin E were able to prevent the expression of the heat shock protein. However, in terms of efficiency, the antioxidant capability of melatonin was clearly higher than that exhibited by vitamin E. The results presented in this study show that antioxidants, especially melatonin, prevent focal regions of injury as assessed by heat shock protein expression in a rat model of SAH. 相似文献
98.
Diez-Ewald M Campos G Rivero F Alvarez L Torres E Arocha-Piñango CL Ryder E Arteaga-Vizcaíno M Vizcaíno G Fernández N 《Investigación clínica》2003,44(1):21-30
The purpose of the present work was to determine the plasma concentrations of fibrinogen and Von Willebrand Factor (VWF) as well as platelet aggregation, in an apparently healthy population of 306 men and 41 women, 33 to 65 years of age, workers of the national oil industry (PDVSA, Maracaibo), as a base investigation in a 5-year prospective national collaborative study. The participants were previously subjected to a thorough clinical examination with cardiovascular evaluation and laboratory tests. Clottable fibrinogen and VWF concentrations were determined in platelet poor plasma, the last one by immunoclectrophoresis, and a multimeric analysis of VWF was performed on those plasmas with concentrations higher than 150 U/dL by SDS agarose electrophoresis, followed by cellulose membrane transference. Platelet aggregation was studied in platelet rich plasma with no addition of stimulants and after collagen and ristocetin were added. Forty per cent of men and 65.8% of women, showed fibrinogen concentrations above 300 mg/dL (p < 0.01) and 12.2% of men and 15.4% of women had VWF values higher than 150 U/dL, with normal multimeric distribution. Fourteen individuals presented spontancous platelet aggregation and increased aggregation in 12 and 13 of them, after induction with collagen and ristocetin respectively. Comparing these findings with those of previous collaborative studies from other countries, the present results could mean that an important proportion of the population here studied, could be at risk for a future coronary event; however, as these are the base findings in Maracaibo, the significance of our results will be better evaluated at the end of the five year study. 相似文献
99.
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
100.
Joven J Arcelús R Camps J Ordóñez-Llanos J Vilella E González-Sastre F Blanco-Vaca F 《Journal of molecular medicine (Berlin, Germany)》2000,78(3):147-154
Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria. 相似文献