全文获取类型
收费全文 | 22512篇 |
免费 | 526篇 |
国内免费 | 528篇 |
专业分类
耳鼻咽喉 | 613篇 |
儿科学 | 1254篇 |
妇产科学 | 393篇 |
基础医学 | 2132篇 |
口腔科学 | 715篇 |
临床医学 | 1514篇 |
内科学 | 5058篇 |
皮肤病学 | 381篇 |
神经病学 | 1542篇 |
特种医学 | 592篇 |
外科学 | 3635篇 |
综合类 | 686篇 |
一般理论 | 10篇 |
预防医学 | 2228篇 |
眼科学 | 498篇 |
药学 | 1451篇 |
8篇 | |
中国医学 | 353篇 |
肿瘤学 | 503篇 |
出版年
2024年 | 18篇 |
2023年 | 69篇 |
2022年 | 102篇 |
2021年 | 118篇 |
2020年 | 129篇 |
2019年 | 151篇 |
2018年 | 181篇 |
2017年 | 89篇 |
2016年 | 176篇 |
2015年 | 145篇 |
2014年 | 216篇 |
2013年 | 157篇 |
2012年 | 2107篇 |
2011年 | 2351篇 |
2010年 | 609篇 |
2009年 | 395篇 |
2008年 | 1816篇 |
2007年 | 2074篇 |
2006年 | 1807篇 |
2005年 | 1939篇 |
2004年 | 1833篇 |
2003年 | 1760篇 |
2002年 | 1622篇 |
2001年 | 1105篇 |
2000年 | 1597篇 |
1999年 | 730篇 |
1998年 | 95篇 |
1997年 | 23篇 |
1996年 | 20篇 |
1995年 | 27篇 |
1994年 | 12篇 |
1993年 | 10篇 |
1992年 | 6篇 |
1991年 | 9篇 |
1990年 | 7篇 |
1989年 | 12篇 |
1988年 | 11篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 3篇 |
1984年 | 2篇 |
1983年 | 5篇 |
1982年 | 5篇 |
1981年 | 4篇 |
1978年 | 1篇 |
1976年 | 1篇 |
1967年 | 1篇 |
1966年 | 1篇 |
1957年 | 1篇 |
1942年 | 2篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
51.
Smaili SS Carvalho SM Cavalcanti PM Jurkiewicz NH García AG Jurkiewicz A 《Pflügers Archiv : European journal of physiology》2001,442(3):376-382
Carbachol-induced contractions of rat stomach fundus strips, obtained in a nutrient solution containing 1.8 mM Ca2+, were resistant to Ca2+ withdrawal, even after 1 h of bathing the tissues in a nominal 0 Ca2+ solution. This was not observed when K+ was used to evoke contractions, which were rapidly inhibited after Ca2+ removal (t1/2=2 min). The effect of carbachol in 0 Ca2+ solution was reduced by using drugs that reduce intracellular pools of Ca2+, such as caffeine (1-3 mM), ryanodine (30 microM) or thapsigargin (1 microM), corroborating the involvement of intracellular Ca2+ stores. On the other hand, when the 0 Ca2+ solution contained EGTA, a complete decline of carbachol effects was observed within about 8 min, indicating the involvement of extracellular Ca2+. Atomic absorption spectrometry showed that our 0 Ca2+ solution still contained 45 microM Ca2+, which was drastically reduced to 5.9 nM in the presence of EGTA. Taken together, our results indicate that the effects of carbachol are due to the mobilization of caffeine-, ryanodine- and thapsigargin-sensitive intracellular Ca2+ stores, and that these stores are not inactivated or depleted if micromolar concentrations (45 microM), but not nanomolar concentrations (5.9 nM) of Ca2+ are maintained in the extracellular milieu. 相似文献
52.
Worldwide genomic diversity of the human papillomaviruses-53, 56, and 66, a group of high-risk HPVs unrelated to HPV-16 and HPV-18 总被引:3,自引:0,他引:3
Prado JC Calleja-Macias IE Bernard HU Kalantari M Macay SA Allan B Williamson AL Chung LP Collins RJ Zuna RE Dunn ST Ortiz-Lopez R Barrera-Saldaña HA Cubie HA Cuschieri K von Knebel-Doeberitz M Sanchez GI Bosch FX Villa LL 《Virology》2005,340(1):95-104
Among more than 200 human papillomavirus (HPV) types presumed to exist, 18 "high-risk" HPV types are frequently found in anogenital cancer. The best studied types are HPV-16 and 18, which are only distantly related to one another and form two separate phylogenetic branches, each including six closely related types. HPV-30, 53, 56, and 66 form a third phylogenetic branch unrelated to HPV-16 and 18. Worldwide comparison of HPV-16 and 18 isolates revealed a distribution of variant genomes that correlated with the geographic origin and the ethnicity of the infected cohort and led to the concept of unique African, European, Asian, and Native American HPV-16 and 18 variants. Here, we address the question whether similar phylogenies are found for HPV-53, 56, and 66 by determining the sequence of the long control regions (LCR) of these HPVs in samples from Europe, Asia, and Africa, and from immigrant societies in North and South America. Phylogenetic trees calculated from point mutations and a few insertions/deletions affecting 2-4.2% of the nucleotide sequences were distinct for each of the three HPVs and divergent from HPV-16 and 18. In contrast to the "star-phylogenies" formed by HPV-16 and 18 variants, 44 HPV-53 isolates represented nine variants, which formed two deep dichotomic branches reminiscent of the beginning split into two new taxa, as recently observed for subtypes of HPV-44 and 68. A total of 66 HPV-56 isolates represented 17 variants, which formed three branches preferentially containing European, Asian, and African variants. Variants of a fourth branch, deeply separated from the other three, were characterized by a 25 bp insertion and created a dichotomy rather than star-like phylogeny. As it contained isolates from cohorts in all continents, it may have evolved before the spread of humans into all continents. 18 of 31 HPV-66 isolates represented the prototype clone, which was found in all parts of the world, while the remaining 13 clones formed 11 branches without any geographic association. Our findings confirm the notion of a quantitatively limited genomic diversity of each HPV type with some correlation to the geographic origin of the sample. In addition, we observed in some variants of these three HPV types mutations that affect the amino acid sequence of the E6 oncoproteins and the L1 capsid protein, supporting the possibility of immunogenic and oncogenic diversity between variants of any HPV type. 相似文献
53.
Emergence of nonencapsulated and encapsulated non-b-type invasive Haemophilus influenzae isolates in Portugal (1989-2001)
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)
Phenotypes and genetic relatedness of invasive Haemophilus influenzae strains were evaluated from 1989 through 2001. Among 119 isolates, multidrug resistance decreased (from 50 to 0%), the level of H. influenzae serotype b (Hib) strains declined (from 81 to 16%), the level of noncapsulated strains rose (from 19 to 80%), and the first invasive H. influenzae serotype f strain was described. This study documents changes in invasive H. influenzae infections in Portugal, i.e., the emergence of non-type-b strains that are genetically diverse and unrelated to Hib. 相似文献
54.
Bcl-x(L)-mediated changes in metabolic pathways of breast cancer cells: from survival in the blood stream to organ-specific metastasis
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)
España L Martín B Aragüés R Chiva C Oliva B Andreu D Sierra A 《The American journal of pathology》2005,167(4):1125-1137
Bcl-x(L) protein plays a role in breast cancer dormancy, promoting survival of cells in metastatic foci by counteracting the proapoptotic signals in the microenvironment. The aim of this study was to identify phenotypes mediated by Bcl-x(L) in breast cancer cells that enhance in vivo survival of clinical metastases. 435/Bcl-x(L) or 435/Neo human breast cancer cells were injected into the inguinal mammary gland of nude mice, and tumors, metastases in lymph node, lung, and bone, and bloodstream surviving cells were examined. Proteomic analysis identified 17 proteins that were overexpressed (more than twofold) or underexpressed (less than twofold) in metastases. A protein interaction program allowed us to functionally associate peroxiredoxin 3, peroxiredoxin 2, carbonyl reductase 3, and enolase 1, suggesting a role for cellular responses to oxidative stress in metastasis organ selection. The prediction included proteins involved in redox systems, kinase pathways, and the ATP synthase complex. Furthermore, the interaction of redox proteins with enolase 1 suggests a connection between glycolysis and antioxidant pathways, enabling achievement of a high metastatic activity. In conclusion, Bcl-x(L) mediates a phenotype in which redox pathways and glycolysis are coupled to protect breast cancer metastatic cells during transit from the primary tumor to the metastatic state. 相似文献
55.
Recombinant cysteine proteinase from Leishmania (Leishmania) chagasi implicated in human and dog T-cell responses
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)
da Costa Pinheiro PH de Souza Dias S Eulálio KD Mendonça IL Katz S Barbiéri CL 《Infection and immunity》2005,73(6):3787-3789
High in vitro lymphoproliferative responses were induced in humans and dogs by a recombinant Leishmania (Leishmania) chagasi cysteine proteinase, with secretion of IFN-gamma in asymptomatic subjects or of IFN-gamma, interleukin 4 (IL-4), and IL-10 in oligosymptomatic subjects. In contrast, responses of symptomatic patients and dogs were lower, with production of IL-4 and IL-10. 相似文献
56.
Azorín D Rodríguez-Peralto JL García-García E Salamanca J 《Virchows Archiv : an international journal of pathology》2003,442(3):298-301
Squamous cell carcinoma is one of the most common malignant cutaneous tumors. Several histological variants have been described; the papillary subtype is one of the most infrequent, with only four cases having being reported previously. We report three new cases of this unusual variant of cutaneous squamous cell carcinoma, review the literature and consider the main differential diagnoses. Polymerase chain reaction performed in our three cases did not demonstrate human papilloma virus infection. 相似文献
57.
We previously demonstrated susceptibility of Leishmania sp. to glibenclamide, a K+-ATP transport blocker which interacts with members of the superfamily of adenosine 5′ triphosphate-binding cassette transporters.
In order to characterize the molecular differences between a sensitive Leishmania strain, NR(Gs), and an experimentally selected glibenclamide-resistant strain, NR(Gr), specific biochemical and functional
parameters have been evaluated both in the wild type and in the resistant strain. Most noteworthy, NR(Gr) exhibit an increased
expression of P-glycoprotein and a decreased activity of functional key enzymes such as acid phosphatase, a prominent virulent
factor of the parasite, and pyruvate kinase, a key control enzyme for both carbohydrate and protein metabolism. The specific
biochemical, metabolic and functional changes observed in the resistant strain correlated with a reduced infectivity of stationary
phase NR(Gr) in J774 macrophages and suggested a mechanism to overcome the effect of glibenclamide.
Received: 21 January 2000 / Accepted: 1 March 2000 相似文献
58.
Desmurget M Vindras P Gréa H Viviani P Grafton ST 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2000,134(3):363-377
Several perceptual studies have shown that the ability to estimate the location of the arm degrades quickly during visual occlusion. To account for this effect, it has been suggested that proprioception drifts when not continuously calibrated by vision. In the present study, we re-evaluated this hypothesis by isolating the proprioceptive component of position sense (i.e., the subjects were forced to rely exclusively on proprioception to locate their hand, which was not the case in earlier studies). Three experiments were conducted. In experiment 1, subjects were required to estimate the location of their unseen right hand, at rest, using a visual spot controlled by the left hand through a joystick. Results showed that the mean accuracy was identical whether the localization task was performed immediately after the positioning of the hand or after a 10-s delay. In experiments 2 and 3, subjects were required to point, without vision of their limb, to visual targets. These two experiments relied on the demonstration that biases in the perception of the initial hand location induced systematic variations of the movement characteristics (initial direction, final accuracy, end-point variability). For these motor tasks, the subjects did not pay attention to the initial hand location, which removed the possible occurrence of confounding cognitive strategies. Results indicated that movement characteristics were, on average, not affected when a 15-s or 20-s delay was introduced between the positioning of the arm at the starting point and the presentation of the target. When considered together, our results suggest that proprioception does not quickly drift in the absence of visual information. The potential origin of the discrepancy between our results and earlier studies is discussed. 相似文献
59.
Enrique E Pineda F Malek T Bartra J Basagaña M Tella R Castelló JV Alonso R de Mateo JA Cerdá-Trias T San Miguel-Moncín Mdel M Monzón S García M Palacios R Cisteró-Bahíma A 《The Journal of allergy and clinical immunology》2005,116(5):1073-1079
BACKGROUND: Food allergy may be life-threatening, and patients affected need to receive accurate diagnoses and treatment. Hazelnut has often been implicated as responsible for allergic reactions, and trace quantities can induce systemic reactions. OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerance of sublingual immunotherapy with a standardized hazelnut extract in patients allergic to hazelnut. METHODS: This was a randomized, double-blind, placebo-controlled study. Inclusion criteria were a history of hazelnut allergy and positive skin prick test and double-blind placebo-controlled food challenge results. Patients were then randomly assigned into 2 treatment groups (hazelnut immunotherapy or placebo). Efficacy was assessed by double-blind, placebo-controlled food challenge after 8 to 12 weeks of treatment. Blood samples were drawn for measurement of specific IgE, IgG(4), and serum cytokines before and after treatment. RESULTS: Twenty-three patients were enrolled and divided into 2 treatment groups. Twenty-two patients reached the planned maximum dose at 4 days. Systemic reactions were observed in only 0.2% of the total doses administered. Mean hazelnut quantity provoking objective symptoms increased from 2.29 g to 11.56 g (P = .02; active group) versus 3.49 g to 4.14 g (placebo; NS). Moreover, almost 50% of patients who underwent active treatment reached the highest dose (20 g), but only 9% in the placebo. Laboratory data showed an increase in IgG(4) and IL-10 levels after immunotherapy in only the active group. CONCLUSION: Our data confirm significant increases in tolerance to hazelnut after sublingual immunotherapy as assessed by double-blind, placebo-controlled food challenge, and good tolerance to this treatment. 相似文献
60.
Histological study of the proximal and distal segments of the embryonic outflow tract and great arteries 总被引:1,自引:0,他引:1
Sánchez Gómez C Pliego Pliego L Contreras Ramos A Angel Munguía Rosas M Salazar García M García Romero HL González Jiménez MA 《The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology》2005,283(1):202-211
The normal development of the ventricular outlets and proximal region of the great arteries is a controversial subject. It is known that the conus, truncus arteriosus (truncus), and aortic sac participate; however, there are some doubts as to the actual prospective fate of the truncus. Some authors propose that it gives origin to the proximal region of the great arteries and that the myocardial cells of its wall become smooth muscle. Nevertheless, others think that the truncus only forms the arterial valve apparatus and that therefore the myocardial cells transform into fibroblasts. As a first approach to beginning to elucidate which process occurs, the aim of this article was to study the histological changes in the wall of these components of the developing heart in chick embryos whose hearts had been labeled at the truncoconal boundary at stage 22HH, tracing the changes up to stage 36HH. Also, the histological constitution of the wall of the pulmonary arterial trunk and its valve apparatus were studied in the posthatching and adult hearts of chickens and rats. The conus and truncus walls were always encircled by a myocardial sleeve from the outset of their development. Between stages 26HH to 28HH, the truncal myocardial cells adjacent to the mesenchymal tissue of the ridges began to lose cell-to-cell contacts and invaded the extracellular matrix. At stage 24HH, the aortic sac began to project into the pericardial cavity and became divided into two channels by the aortic-pulmonary septum at stage 26HH. The wall of the aortic sac is mostly constituted by a compact mesenchymal tissue. Initially, it does not have smooth muscle but this starts to appear at stage 30HH. The insertion ring of the valves, a broad structure, was formed by mesenchymal tissue. Both structures were always covered by a myocardial sleeve. The leaflets developed from the truncal ridges, the segment immediately proximal to the aortic sac. Our results indicate that the proximal region of the pulmonary and aortic arteries do not originate from the truncus arteriosus; rather, we found that they take origin from the aortic sac. Thus, our findings agree with the proposal that the myocardial cells of the external sleeve of the truncus become fibroblastic and suggest that the insertion ring of the arterial valves has a dual origin: fibroblasts produced by truncal myocardial transdiferentiation and the mesenchymal tissue of the proximal region of the truncal ridges, while the leaflets have their origin from the truncal ridges. We discuss the fact that, because the truncus arteriosus does not give origin to the trunks of the aortic and pulmonary arteries, it may be necessary to modify terminology. Based on our results, together with the new findings obtained by in vivo labeling, immunostaining, a chimeric approach, and ultrastructural studies, we propose a developmental model that correlates the fate of the conus, truncus, and aortic sac with the normal morphogenesis of the ventricular outlet tracts and the trunks of the great arteries. (c) 2005 Wiley-Liss, Inc. 相似文献