全文获取类型
收费全文 | 6053篇 |
免费 | 442篇 |
国内免费 | 57篇 |
专业分类
耳鼻咽喉 | 26篇 |
儿科学 | 133篇 |
妇产科学 | 114篇 |
基础医学 | 938篇 |
口腔科学 | 103篇 |
临床医学 | 579篇 |
内科学 | 1572篇 |
皮肤病学 | 103篇 |
神经病学 | 732篇 |
特种医学 | 153篇 |
外科学 | 500篇 |
综合类 | 14篇 |
一般理论 | 1篇 |
预防医学 | 381篇 |
眼科学 | 65篇 |
药学 | 489篇 |
中国医学 | 13篇 |
肿瘤学 | 636篇 |
出版年
2024年 | 6篇 |
2023年 | 66篇 |
2022年 | 158篇 |
2021年 | 268篇 |
2020年 | 131篇 |
2019年 | 166篇 |
2018年 | 231篇 |
2017年 | 166篇 |
2016年 | 187篇 |
2015年 | 244篇 |
2014年 | 276篇 |
2013年 | 315篇 |
2012年 | 530篇 |
2011年 | 547篇 |
2010年 | 272篇 |
2009年 | 242篇 |
2008年 | 428篇 |
2007年 | 446篇 |
2006年 | 383篇 |
2005年 | 380篇 |
2004年 | 322篇 |
2003年 | 324篇 |
2002年 | 244篇 |
2001年 | 31篇 |
2000年 | 13篇 |
1999年 | 17篇 |
1998年 | 29篇 |
1997年 | 25篇 |
1996年 | 23篇 |
1995年 | 14篇 |
1994年 | 15篇 |
1993年 | 12篇 |
1992年 | 7篇 |
1991年 | 10篇 |
1990年 | 5篇 |
1989年 | 3篇 |
1988年 | 4篇 |
1986年 | 1篇 |
1985年 | 1篇 |
1984年 | 1篇 |
1983年 | 1篇 |
1982年 | 1篇 |
1980年 | 1篇 |
1979年 | 1篇 |
1971年 | 1篇 |
1970年 | 1篇 |
1969年 | 2篇 |
1918年 | 1篇 |
排序方式: 共有6552条查询结果,搜索用时 0 毫秒
21.
Pietro Maria Donisi Nadia Di Lorenzo Manuela Riccardi Alessandro Paparella Claudia Sarpellon Simona Zupo Giovanni Bertoldero Claudia Minotto Vincenzo Stracca-Pansa 《Diagnostic molecular pathology》2006,15(4):206-215
We analyzed individual VH gene rearrangements in 55 consecutive B-chronic lymphocytic leukemia (B-CLL) patients collected from a northeastern region of Italy, stressing the possible differences related to geographic characteristics of the cohorts studied. Considering the percentage of somatic mutations present in the VH gene sequences and using the 98% cut-off value, 38 of the 55 B-CLL (69%) patients displayed somatic hypermutations and 17 (31%) had a germline configuration. Our results confirm and extend the observations of a bias in the use of certain VH, DH, and JH genes among B-CLL cells. The most frequently used VH genes were VH1-69 (12.7%) with VH3-23 (12.7%) and VH4-34 (10.9%). Collectively these genes accounted for 36.3% of the cases. In the mutated cases, the range of mutations varied from 2% to 15%, with a median of 6.5%. VH1-69 (7 cases, all unmutated) carried few mutations as opposed to VH3-23 (7 cases, 5 of which mutated), VH4-34 (6 cases, all mutated), and VH3-30 (5 cases, all mutated), which show a high load of mutations. D3 family genes were found frequently (38.1%) followed by D2 (27.2%) and D6 (18.1%). The individual D segment most frequently used was D3-3, which was present in 16.3% of cases. There was predominance of the JH4 gene (49%) followed by JH6 (40%). Analysis of the distribution of replacement and silent mutations in the mutated sequences using the method of Lossos showed in 39.4% of cases evidence of antigen selection in the framework region and/or complementary determining regions. In comparison with a recent study on B-CLL patients from the Mediterranean area, the VH4-34 gene was significantly overused in the mutated group at a percentage double that of the Italian cohort reported in this study (10.9% vs. 5%), but at a frequency similar to the entire Mediterranean region (10.7%). We also found an over-representation of VH1-69 usage in the germline group, at a frequency (12.7%) higher than previously described by the same authors (Italian 8%, Mediterranean 10.7%). On the contrary, VH3-07 and VH3-49 were not much used in our study (5.4% and 1.8%, respectively) compared with the Italian group (8% and 5.1%). In our study, VH3-23 gene segment was frequently expressed, at frequency as high as that of VH1-69, a finding in keeping with reported B-CLL Italian data, but higher than the entire series of the Mediterranean area (12.7% vs. 9.2%); VH3-21 gene, frequently expressed in northern European CLL but rarely in the Mediterranean area, was completely absent. This biased usage of VH family genes may reflect a geographic leukemic repertoire, perhaps owing to a peculiar genetic background, depending on variations in germline composition of the IgVH locus or to the effect of a potential environmental element less frequently encountered in different regions. 相似文献
22.
Simona Picchietti Francesca Renata Terribili Lucia Mastrolia Giuseppe Scapigliati L. Abelli 《Brain structure & function》1997,196(6):457-463
The monoclonal antibodies DLT15 and DLIg3, which recognize antigenic determinants expressed by T cells and Ig-bearing cells, respectively, allowed the development of gut-associated lymphoid tissue of the teleost fish Dicentrarchus labrax (L.) to be studied. DLT15- immunoreactive cells were first detected in the epithelium of the stomach and intestine at day 30 post-hatching of fish maintained at 16° C. At that age, positive cells were found only in the thymus. Between day 44 and day 81 post-hatching, DLT15-immunoreactive cells became numerous, both in and under the gut epithelium. A gradient in the number of lymphocytes was present, concentrating them towards the anus. Until day 81 post-hatching, DLIg3-immunoreactive cells were not found in the gut, although they were present in the kidney, spleen and thymus earlier. Infrequent Ig-bearing cells were found in the gut mucosa of 1-year-old sea bass. This study showed that the gut-associated lymphoid tissue developed earlier than other lymphoid compartments. It also provided evidence of the predominance of T cells in the gut immune system of the sea bass. 相似文献
23.
Bianciardi P Fasanella A Foglia Manzillo V Trotta T Pagano A Sorino S Gradoni L Oliva G 《Parasitology research》2004,93(6):486-492
We evaluated the efficacy of enrofloxacin, alone or combined with metronidazole, against Leishmania infantum. The in vitro activity of this fluoroquinolone was assessed using two different methods: a direct test aimed at assessing the drug activity on the parasite, and an indirect test aimed at evaluating the drug effect on macrophage killing, lymphomonocyte activation and nitric oxide production. An in vivo test was also performed on 36 dogs with leishmaniasis, subdivided into three groups, one treated with enrofloxacin, another with enrofloxacin plus metronidazole, and a control group with meglumine antimoniate. The direct test did not show any action of enrofloxacin on the parasite, while the indirect testing showed an enhancement of macrophage killing and an increase in nitric oxide production. These findings show that enrofloxacin does not exert a direct anti-leishmanial activity in vitro. However, on the basis of the positive immunostimulation results shown in vitro and the clinical improvement, particularly of the cutaneous lesions, obtained in several dogs in the in vivo trial, the use of enrofloxacin in association with a specific anti-leishmanial drug can be proposed in the therapeutic protocol of canine leishmaniasis. 相似文献
24.
The effects of sodium arsenite at a sub-MIC concentration (25 mg/l) upon different bacterial functions were studied. This compound reduced the killing activity of nalidixic acid, amikacin, and meropenem. It also promoted the loss of F'lac from bacterial hosts and increased the number of recombinants in conjugation and transduction experiments. Transposition of Tn9 was also enhanced by the salt. In addition, sodium arsenite abolished the lethal effect of temperature on thermosusceptible DNA synthesis mutants in a similar manner to that seen in an anaerobic environment. Finally at a low dose, it induced the SOS response, and the related production of recA-dependent enzymes was reduced as the sodium arsenite concentration increased. It has been suggested that arsenite primarily affects the uvrA gene product, influencing the other bacterial functions studied. The energetic depletion caused by this compound appears to play a role in the activity of autolytic enzymes. 相似文献
25.
Lipid abnormalities in HIV-infected patients are not correlated with lopinavir plasma concentrations
26.
Francesca Blasi Elena Bacchelli Giulia Pesaresi Simona Carone Anthony J Bailey Elena Maestrini 《American journal of medical genetics. Part B, Neuropsychiatric genetics》2006,(3):220-221
Neuroligin abnormalities have been recently implicated in the aetiology of autism spectrum disorders (ASD), given the finding of point mutations in the two X-linked genes NLGN3 and NLGN4X and the important role of neuroligins in synaptogenesis. To enquire on the relevance and frequency of neuroligin mutations in ASD, we performed a mutation screening of NLGN3 and NLGN4X in a sample of 124 autism probands from the International Molecular Genetic Study of Autism Consortium (IMGSAC). We identified a new non-synonymous variant in NLGN3 (Thr632Ala), which is likely to be a rare polymorphism. Our data indicate that coding mutations in these genes are very rarely associated to ASD. 相似文献
27.
Mariella Dono Simona Zupo Raffaella Masante Giuseppe Taborellin Nicholas Chiorazzp Manlio Ferrarini 《European journal of immunology》1993,23(4):873-881
This study investigated the response of different CD5? B cell subsets to CD40 monoclonal antibody (mAb) in various combinations with interleukin (IL)-4 or rabbit anti-human μ chain antibody (a-μ-Ab). The different CD5 B cell subsets were isolated from tonsillar B cell suspensions depleted of CD5+ B cells and subsequently fractionated on Percoll density gradients. While resting CD5+ B cells proliferated and produced IgM molecules in response to a-μ-Ab, IL-4 and CD40 mAb as well as to Staphylococcus aureus Cowan strain I (SAC) and IL-2, resting CD5? B cells, which were co-purified in the same 60% Percoll fractions, consistently failed to respond. These cells were, however, activated by the stimuli employed, as demonstrated by their capacity to express the surface activation markers CD69, CD25 and CD71. Resting CD5+ B cells had the typical phenotype of mantle zone B cells (IgM+ IgD+ CD39+ CD38? CD10? CDw75dim), whereas resting CD5? B cells were CD38? CD39? CD 10? CDw75 intermediate and expressed surface IgM but relatively little surface IgD and could not be classified as mantle zone or germinal center cells. The finding that purified germinal center cells (CD38+ CD10+ CD39? CDw75bright, IgG+) responded to CD40 mAb and IL-4 and also to SAC plus IL-2 further underlined the differences to resting CD5? B cells. However, some of the data collected suggest possible relationships between CD5? B cells and germinal center cells. The CD5? B cells isolated from the 50 % Percoll fraction proliferated in response to a-μ-Ab, CD40 mAb and IL-4 as well as to SAC and IL-2. These cells had the same mantle zone B cell phenotype as the CD5+ B cells, but their capacity to respond to the stimuli in vitro was unrelated to a possible contamination with CD5+ B cells, as documented by the appropriate controls. Furthermore, upon exposure to SAC or phorbol esters, the large majority of CD5? B cells from the 50 % Percoll fraction did not express surface CD5 and there was very little if any accumulation of CD5 mRNA. Finally, most of the cycling cells in the stimulated CD5? B cells did not express CD5. The CD5? B cells from the 50 % Percoll fraction were comprised of a consistent proportion of cells that expressed surface activation markers. The removal of these cells abrogated the capacity of the suspensions to respond to the stimuli in vitro, possibly suggesting that these cells additional activation signals in vivo which were essential to acquire the capacity to respond and that could not be reproduced in vitro. The present study underlines the phenotypic and functional heterogeneity of CD5? B cells and contributes to the identification of two subsets of these cells which differ in phenotype, tissue distribution and in vitro responses to different stimuli. 相似文献
28.
Mazzanti L Cicognani A Baldazzi L Bergamaschi R Scarano E Strocchi S Nicoletti A Mencarelli F Pittalis M Forabosco A Cacciari E 《American journal of medical genetics. Part A》2005,135(2):150-154
The identification of Y-chromosome material is important in females with Ullrich-Turner syndrome (UTS) due to the risk of developing gonadoblastoma or other gonadal tumors. There is controversy regarding the frequency of the Y-chromosome-derived material and the occurrence of gonadoblastoma in these patients. The aim of our study was to evaluate a large number of patients with UTS, followed before and during the pubertal age for the prevalence of Y-chromosome derived material, the occurrence of gonadoblastoma, and the incidence of possible neoplastic degeneration. An unselected series of 171 patients with UTS (1-34 years old), diagnosed cytogenetically, was studied for Y-chromosome markers (SRY and Y-centromeric DYZ3 repeats). The follow-up was of 2-22 years; 101 of these patients were followed during pubertal age. Y-chromosome material was found in 14 patients (8%): 12 of these were gonadectomized (2.8-25.9 years). A gonadoblastoma was detected in four patients under 16 years of age: in two, Y-material was detected only at molecular analysis (at conventional cytogenetic analysis, one was included in the 45,X group and one in the X + mar group) and one had also an immature teratoma and an endodermal sinus carcinoma. The prevalence of gonadoblastoma in our series of gonadectomized UTS patients with Y-positive material was of 33.3% (4/12). Our data suggest that the age of appearance and the possibility of malignant degeneration of gonadoblastoma can occur early in life. These patients, in particular those with 45,X or a marker chromosome may benefit from molecular screening to detect the presence of Y-chromosome material; PCR is a rapid and inexpensive technique. At the moment, laparoscopy and preventive gonadectomy performed as soon as possible remain the procedures of choice for patients with UTS, when Y-chromosome has been identified, as we are still unable to predict a future malignant evolution of gonadoblastoma. 相似文献
29.
Simona Gurzu Tivadar Bara Calin Molnar Tivadar Bara Vlad Butiurca Hanga Beres Simin Savoji Ioan Jung 《Pathology, research and practice》2019,215(1):82-89
Background
Pancreatic mucinous cystic neoplasms (MCN) are rare tumors that are usually diagnosed in females.Materials and methods
In our department, only four of the 109 consecutive cases of pancreatic tumors (3.67%) were diagnosed as MCNs. In this report, we present the characteristics of these four specific cases which also showed unusual HER-2 positivity and neuroendocrine differentiation.Results
The four MCNs were diagnosed in patients with ages between 46 and 75 years. Other clinical particularities were the following: one benign case, splenic rupture as result of a giant cystic tumor on the tail of the pancreas directly invading the spleen in the second one, metastases in the accessory spleen in the third one and invasion of the abdominal vessels in the fourth case. In all of these cases, the ovarian-like stroma tested positivity for calretinin, progesterone receptor (PR) and, in cases 2 and 3, for AE1/AE3 keratin. The malignant tumor cells were marked by carcinoembryonic antigen, HER-2, maspin, PR and the neuroendocrine markers synaptophysin, CD56, and neuron-specific enolase.Conclusions
These cases highlight the unusually aggressive behavior of pancreatic MCN with invasive carcinomas that share mixed exo- and endocrine components and show epithelial-mesenchymal transition. 相似文献30.
IL-21 induces both rapid maturation of human CD34+ cell precursors towards NK cells and acquisition of surface killer Ig-like receptors 总被引:9,自引:0,他引:9
Sivori S Cantoni C Parolini S Marcenaro E Conte R Moretta L Moretta A 《European journal of immunology》2003,33(12):3439-3447
The NK cell maturation from CD34(+) Lin(-) hematopoietic cell precursors is a complex process that requires the direct contact with stromal cells and/or the synergistic effect of different cytokines. In this study we show that IL-21 is capable of inducing an accelerated NK cell maturation when added to cultures of CD34(+) Lin(-) cells isolated from human cord blood supplemented with IL-15, Flt3-L and SCF. After 25 days of culture, 50% of CD56(+) cells expressed various NK cell markers including the NKp46 and NKp30 triggering receptors, the CD94/NKG2A inhibitory receptor and CD16. At day 35, substantial fractions of NK cells expressed KIR, CD8 and CD2, i.e. surface markers expressed by mature NK cells, that are virtually undetectable in developing NK cells cultured in the absence of IL-21. Remarkably, similar to mature NK cells all these markers were included in the CD56(dim) cell fraction, while the CD56(bright) population was only composed of CD94/NKG2A(-) and CD94/NKG2A(+) cells. Thus, IL-21 allows the induction of a full NK cell maturation in vitro and offers an important tool for dissecting the molecular mechanisms involved in different steps of NK cell maturation and in the acquisition of a mature KIR repertoire. 相似文献