全文获取类型
收费全文 | 9376篇 |
免费 | 876篇 |
国内免费 | 42篇 |
专业分类
耳鼻咽喉 | 114篇 |
儿科学 | 310篇 |
妇产科学 | 221篇 |
基础医学 | 1453篇 |
口腔科学 | 245篇 |
临床医学 | 787篇 |
内科学 | 2091篇 |
皮肤病学 | 251篇 |
神经病学 | 970篇 |
特种医学 | 296篇 |
外国民族医学 | 1篇 |
外科学 | 1347篇 |
综合类 | 48篇 |
一般理论 | 1篇 |
预防医学 | 736篇 |
眼科学 | 138篇 |
药学 | 623篇 |
中国医学 | 19篇 |
肿瘤学 | 643篇 |
出版年
2023年 | 52篇 |
2022年 | 122篇 |
2021年 | 239篇 |
2020年 | 158篇 |
2019年 | 250篇 |
2018年 | 316篇 |
2017年 | 216篇 |
2016年 | 237篇 |
2015年 | 249篇 |
2014年 | 304篇 |
2013年 | 428篇 |
2012年 | 550篇 |
2011年 | 551篇 |
2010年 | 343篇 |
2009年 | 264篇 |
2008年 | 438篇 |
2007年 | 430篇 |
2006年 | 467篇 |
2005年 | 419篇 |
2004年 | 384篇 |
2003年 | 315篇 |
2002年 | 331篇 |
2001年 | 316篇 |
2000年 | 305篇 |
1999年 | 250篇 |
1998年 | 94篇 |
1997年 | 99篇 |
1996年 | 82篇 |
1995年 | 92篇 |
1994年 | 68篇 |
1993年 | 49篇 |
1992年 | 204篇 |
1991年 | 176篇 |
1990年 | 165篇 |
1989年 | 165篇 |
1988年 | 146篇 |
1987年 | 112篇 |
1986年 | 107篇 |
1985年 | 103篇 |
1984年 | 94篇 |
1983年 | 59篇 |
1982年 | 41篇 |
1981年 | 30篇 |
1980年 | 32篇 |
1979年 | 60篇 |
1978年 | 32篇 |
1976年 | 28篇 |
1974年 | 40篇 |
1973年 | 34篇 |
1971年 | 31篇 |
排序方式: 共有10000条查询结果,搜索用时 46 毫秒
71.
Mohan D Rao GR Swalsky PA Bakker A Martinez AJ Finkelstein SD 《Archives of pathology & laboratory medicine》2004,128(10):1161-1164
A 22-year-old man with previous radiation treatment for childhood astrocytoma underwent resection of a right parietooccipital lesion. Histopathology revealed a malignant neoplasm with areas of astrocytic and primitive neuroectodermal components. To resolve the relationship and cellular origin, representative tissue was microdissected from several targets, obtaining a balanced mixture of each element. Nonneoplastic brain parenchyma was separately microdissected to determine polymorphic marker informativeness and to serve as an internal negative control. Despite the relatively small quantity of tissue removed for each microdissection target, sufficient material was available for reliable, balanced, polymerase chain reaction-format genotyping encompassing a panel of tumor suppressor genes and genetic loci associated with these forms of neoplasia. The findings revealed distinct discordant genotypic profiles for each of the neoplastic components. The efficacy of the approach used for molecular analysis of this complex neoplasm and the implication of the genotypic findings are discussed. 相似文献
72.
Paul Kruszka Tommy Hu Sungkook Hong Rebecca Signer Benjamin Cogné Betrand Isidor Sarah E. Mazzola Jacques C. Giltay Koen L. I. van Gassen Eleina M. England Lynn Pais Charlotte W. Ockeloen Pedro A. Sanchez‐Lara Esther Kinning Darius J. Adams Kayla Treat Wilfredo Torres‐Martinez Maria F. Bedeschi Maria Iascone Stephanie Blaney Oliver Bell Tiong Y. Tan Marie‐Ange Delrue Julie Jurgens Brenda J. Barry Elizabeth C. Engle Sarah K. Savage Nicole Fleischer Julian A. Martinez‐Agosto Kym Boycott Elaine H. Zackai Maximilian Muenke 《American journal of medical genetics. Part A》2019,179(10):2075-2082
Zinc finger protein 462 (ZNF462) is a relatively newly discovered vertebrate specific protein with known critical roles in embryonic development in animal models. Two case reports and a case series study have described the phenotype of 10 individuals with ZNF462 loss of function variants. Herein, we present 14 new individuals with loss of function variants to the previous studies to delineate the syndrome of loss of function in ZNF462. Collectively, these 24 individuals present with recurring phenotypes that define a multiple congenital anomaly syndrome. Most have some form of developmental delay (79%) and a minority has autism spectrum disorder (33%). Characteristic facial features include ptosis (83%), down slanting palpebral fissures (58%), exaggerated Cupid's bow/wide philtrum (54%), and arched eyebrows (50%). Metopic ridging or craniosynostosis was found in a third of study participants and feeding problems in half. Other phenotype characteristics include dysgenesis of the corpus callosum in 25% of individuals, hypotonia in half, and structural heart defects in 21%. Using facial analysis technology, a computer algorithm applying deep learning was able to accurately differentiate individuals with ZNF462 loss of function variants from individuals with Noonan syndrome and healthy controls. In summary, we describe a multiple congenital anomaly syndrome associated with haploinsufficiency of ZNF462 that has distinct clinical characteristics and facial features. 相似文献
73.
Lysozyme was isolated from Bacillus Calmette-Guerin-elicited rabbit alveolar macrophages by acid extraction and purified to homogeneity by a single-column procedure. Yields of the purified enzyme averaged between 20 and 30 mg per rabbit, values far in excess of those obtained with previously published methods. Rabbit lysozyme has a molecular weight of 14,300 and exhibits optimal lytic activity against Micrococcus lysodeikticus at an ionic strength of 0.04, pH 6.5. Our results indicate that lysozyme and other granule components can be fractionated from elicited alveolar macrophages by using simple techniques, suggesting methods for the bulk purification of lysosomal constituents. 相似文献
74.
Soluble factors released by Toxoplasma gondii-infected astrocytes down-modulate nitric oxide production by gamma interferon-activated microglia and prevent neuronal degeneration
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rozenfeld C Martinez R Figueiredo RT Bozza MT Lima FR Pires AL Silva PM Bonomo A Lannes-Vieira J De Souza W Moura-Neto V 《Infection and immunity》2003,71(4):2047-2057
The maintenance of a benign chronic Toxoplasma gondii infection is mainly dependent on the persistent presence of gamma interferon (IFN-gamma) in the central nervous system (CNS). However, IFN-gamma-activated microglia are paradoxically involved in parasitism control and in tissue damage during a broad range of CNS pathologies. In this way, nitric oxide (NO), the main toxic metabolite produced by IFN-gamma-activated microglia, may cause neuronal injury during T. gondii infection. Despite the potential NO toxicity, neurodegeneration is not a common finding during chronic T. gondii infection. In this work, we describe a significant down-modulation of NO production by IFN-gamma-activated microglia in the presence of conditioned medium of T. gondii-infected astrocytes (CMi). The inhibition of NO production was paralleled with recovery of neurite outgrowth when neurons were cocultured with IFN-gamma-activated microglia in the presence of CMi. Moreover, the modulation of NO secretion and the neuroprotective effect were shown to be dependent on prostaglandin E(2) (PGE(2)) production by T. gondii-infected astrocytes and autocrine secretion of interleukin-10 (IL-10) by microglia. These events were partially eliminated when infected astrocytes were treated with aspirin and cocultures were treated with anti-IL-10 neutralizing antibodies and RP-8-Br cyclic AMP (cAMP), a protein kinase A inhibitor. Further, the modulatory effects of CMi were mimicked by the presence of exogenous PGE(2) and by forskolin, an adenylate cyclase activator. Altogether, these data point to a T. gondii-triggered regulatory mechanism involving PGE(2) secretion by astrocytes and cAMP-dependent IL-10 secretion by microglia. This may reduce host tissue inflammation, thus avoiding neuron damage during an established Th1 protective immune response. 相似文献
75.
The in vitro bactericidal reaction of human plasma serum against Bacillus subtilis was investigated. Human lysozyme was purified to homogeneity, and antiserum was prepared against the enzyme. The anti-lysozyme immunoglobulin G was used as a specific inhibitor in bactericidal and bacteriolytic reactions. It was found that at low serum concentrations lysozyme was the primary bactericide active against B. subtilis. At appreciably higher serum concentrations, a lysozyme-independent bactericidal activity was also demonstrated. 相似文献
76.
Purification and characterization of Clostridium sordellii hemorrhagic toxin and cross-reactivity with Clostridium difficile toxin A (enterotoxin). 总被引:3,自引:3,他引:3
下载免费PDF全文
![点击此处可从《Infection and immunity》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Hemorrhagic toxin (toxin HT) was purified from Clostridium sordellii culture filtrate. The purification steps included ultrafiltration through an XM-100 membrane filter and immunoaffinity chromatography, using a monoclonal antibody to toxin A of Clostridium difficile as the ligand. Toxin HT migrated as a major band with a molecular weight of 525,000 and a minor band at 450,000 on nondenaturing gradient polyacrylamide gel electrophoresis. The molecular weight was estimated at 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Isoelectric focusing indicated an apparent pI of 6.1. Toxin HT was cytotoxic for cultured cells and lethal for mice by intraperitoneal injection, and it elicited an accumulation of hemorrhagic fluid in rabbit ileal loops. Immunodiffusion analysis revealed a reaction of partial identity between toxins A and HT. Immunological cross-reactivity between these toxins was further demonstrated by immunoblotting and by neutralization of toxin HT biological activity with antibodies to toxin A. A sensitive indirect enzyme-linked immunosorbent assay was used to examine the affinity involved in homologous and heterologous antigen-antibody interactions. Our findings show that toxin HT has biological activities and immunological properties similar to those of toxin A; however, the toxins are not identical. 相似文献
77.
78.
Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole
下载免费PDF全文
![点击此处可从《Journal of clinical microbiology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Martinez M López-Ribot JL Kirkpatrick WR Coco BJ Bachmann SP Patterson TF 《Journal of clinical microbiology》2002,40(9):3135-3139
Candida dubliniensis is an opportunistic yeast that has been increasingly implicated in oropharyngeal candidiasis (OPC) in human immunodeficiency virus (HIV)-infected patients but may be underreported due to its similarity with Candida albicans. Although most C. dubliniensis isolates are susceptible to fluconazole, the inducibility of azole resistance in vitro has been reported. Thus, the use of fluconazole prophylaxis in the treatment of these patients may have contributed to the increasing rates of isolation of C. dubliniensis. In this study, yeast strains were collected from the oral cavities of HIV-infected patients enrolled in a longitudinal study of OPC. Patients received fluconazole for the suppression or treatment of OPC, and isolates collected at both study entry and end of study were chosen for analysis. Samples were plated on CHROMagar Candida medium for initial isolation and further identified by Southern blot analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C. dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study entry, susceptible C. albicans isolates were recovered from oral samples in 42 patients who were followed longitudinally (1 to 36 months). C. albicans strains from 12 of these patients developed fluconazole resistance (fluconazole MIC, >/=64 micro g/ml). C. dubliniensis was not detected at end of study in any of these patients. Of the remaining 30 patients, eight (27%) demonstrated a replacement of C. albicans by C. dubliniensis when a comparison of isolates obtained at baseline and those from the last culture was done. For the 22 of these 30 patients in whom no switch in species was detected, the fluconazole MICs for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 micro g/ml. For the eight patients in whom a switch to C. dubliniensis was detected, the fluconazole MICs for C. dubliniensis isolates at end of study ranged from 0.25 to 64 micro g/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 micro g/ml and those for the other two were 32 and 64 micro g/ml, respectively. In conclusion, a considerable number of patients initially infected with C. albicans strains that failed to develop fluconazole resistance demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be underestimated due to lack of identification and may occur due to the impact of fluconazole on the ecology of oral yeast species. 相似文献
79.
Toxoplasma gondii prevents neuron degeneration by interferon-gamma-activated microglia in a mechanism involving inhibition of inducible nitric oxide synthase and transforming growth factor-beta1 production by infected microglia 总被引:2,自引:0,他引:2
下载免费PDF全文
![点击此处可从《The American journal of pathology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Rozenfeld C Martinez R Seabra S Sant'anna C Gonçalves JG Bozza M Moura-Neto V De Souza W 《The American journal of pathology》2005,167(4):1021-1031
Interferon (IFN)-gamma, the main cytokine responsible for immunological defense against Toxoplasma gondii, is essential in all infected tissues, including the central nervous system. However, IFN-gamma-activated microglia may cause tissue injury through production of toxic metabolites such as nitric oxide (NO), a potent inducer of central nervous system pathologies related to inflammatory neuronal disturbances. Despite potential NO toxicity, neurodegeneration is not commonly found during chronic T. gondii infection. In this study, we describe decreased NO production by IFN-gamma-activated microglial cells infected by T. gondii. This effect involved strong inhibition of iNOS expression in IFN-gamma-activated, infected microglia but not in uninfected neighboring cells. The inhibition of NO production and iNOS expression were parallel with recovery of neurite outgrowth when neurons were co-cultured with T. gondii-infected, IFN-gamma-activated microglia. In the presence of transforming growth factor (TGF)-beta1-neutralizing antibodies, the beneficial effect of the parasite on neurons was abrogated, and NO production reverted to levels similar to IFN-gamma-activated uninfected co-cultures. In addition, we observed Smad-2 nuclear translocation, a hallmark of TGF-beta1 downstream signaling, in infected microglial cultures, emphasizing an autocrine effect restricted to infected cells. Together, these data may explain a neuropreservation pattern observed during immunocompetent host infection that is dependent on T. gondii-triggered TGF-beta1 secretion by infected microglia. 相似文献
80.
J. Garritano C. Martinez K. Grossman P. Intemann K. Merritt R. Pfoff T. Smock 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1996,112(1):35-40
We tested the role of C5 segment inspiratory interneurons in transcribing central respiratory drive to phrenic motoneurons and mediating intersegmental reflexes by cross-correlating the spontaneous activity of 26 interneurons with that of the ipsi -and contralateral C5 phrenic nerves in decerebrate cats. There were 10 interneurons that discharged only during inspiration (phrenic burst) and 16 that discharged tonically with increased firing during inspiration. Of the cross-correlograms for 26 of the interneurons with the ipsilateral phrenic, 20 were flat and 2 had peaks centred about time zero, interpreted as a common activation of the interneurons and motoneurons. The cross-correlograms for 4 other interneurons had troughs centred about time zero, interpreted as a synchronous excitation of the interneurons and inhibition of the motoneurons. Of the cross-correlograms for 23 interneurons with the contralateral phrenic, 22 were flat and 1 had a peak centred about time zero, interpreted as a common activation of the interneuron and motoneurons. Nine of ten cross-correlograms between pairs of interneurons were flat; one had a peak centred about time zero. We conclude that, despite their inspiratory modulated discharge patterns, there is no evidence from this study that the C5 segment inspiratory interneurons convey central respiratory drive to C5 phrenic motoneurons. 相似文献