全文获取类型
收费全文 | 776篇 |
免费 | 42篇 |
国内免费 | 14篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 22篇 |
妇产科学 | 17篇 |
基础医学 | 121篇 |
口腔科学 | 19篇 |
临床医学 | 53篇 |
内科学 | 193篇 |
皮肤病学 | 17篇 |
神经病学 | 31篇 |
特种医学 | 138篇 |
外科学 | 46篇 |
综合类 | 8篇 |
预防医学 | 44篇 |
眼科学 | 12篇 |
药学 | 56篇 |
中国医学 | 5篇 |
肿瘤学 | 49篇 |
出版年
2023年 | 2篇 |
2022年 | 5篇 |
2021年 | 7篇 |
2020年 | 13篇 |
2019年 | 14篇 |
2018年 | 12篇 |
2017年 | 11篇 |
2016年 | 7篇 |
2015年 | 15篇 |
2014年 | 16篇 |
2013年 | 27篇 |
2012年 | 41篇 |
2011年 | 29篇 |
2010年 | 23篇 |
2009年 | 24篇 |
2008年 | 36篇 |
2007年 | 42篇 |
2006年 | 27篇 |
2005年 | 21篇 |
2004年 | 28篇 |
2003年 | 16篇 |
2002年 | 14篇 |
2001年 | 20篇 |
2000年 | 26篇 |
1999年 | 31篇 |
1998年 | 26篇 |
1997年 | 27篇 |
1996年 | 28篇 |
1995年 | 11篇 |
1994年 | 19篇 |
1993年 | 9篇 |
1992年 | 12篇 |
1991年 | 12篇 |
1990年 | 12篇 |
1989年 | 12篇 |
1988年 | 14篇 |
1987年 | 11篇 |
1986年 | 15篇 |
1985年 | 16篇 |
1984年 | 8篇 |
1983年 | 17篇 |
1982年 | 18篇 |
1981年 | 15篇 |
1980年 | 11篇 |
1979年 | 3篇 |
1978年 | 6篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1970年 | 1篇 |
1968年 | 1篇 |
排序方式: 共有832条查询结果,搜索用时 234 毫秒
11.
Arancha C Ruíz-Llorente S Cascón A Osorio A Martínez-Delgado B Benítez J Robledo M 《Journal of human genetics》2002,47(4):190-195
Until now, the study of the multiple endocrine neoplasia type 1 (MEN1) gene in patients suspected of having the disease was expensive and laborious due to the large size of the gene. We have
optimized the conformation-sensitive gel electrophoresis (CSGE) technique to analyze by four rather simple multiplex PCR reactions,
and a single electrophoresis run, the entire coding region of the MEN1 gene, plus the exon–intron boundaries. This improvement of the CSGE technique was confirmed as an effective procedure for
screening for the MEN1 gene by detecting ten previously known MEN1 gene mutations and four polymorphisms. The MEN1 gene of 12 patients with unknown mutations was then screened, and an abnormal CSGE profile was identified in 10/12 cases.
Subsequent DNA sequencing demonstrated 3 of them to be novel mutations (E45K, 4479delACAG, 6073insC) and 7 to have been previously
reported; in the remaining 2 patients, we confirmed the absence of any alteration of the coding sequence of MEN1. Mutation screening of the MEN1 gene using CSGE was demonstrated to be a fast, simple, and inexpensive method to study patients suspected of having MEN1
disease.
Received: November 29, 2001 / Accepted: January 28, 2002 相似文献
12.
Dohle GR; Ramos L; Pieters MH; Braat DD; Weber RF 《Human reproduction (Oxford, England)》1998,13(3):620-623
Male genital tract obstructions may result from infections, previous
inguinal and scrotal surgery (vasectomy) and congenital bilateral absence
of the vas deferens (CBAVD). Microsurgery can sometimes be successful in
treating the obstruction. In other cases and in cases of failed surgical
intervention, the patient can be treated by microsurgical or percutaneous
epididymal sperm aspiration (MESA, PESA) or testicular sperm extraction
(TESE) and intracytoplasmic sperm injection (ICSI). We present the results
of 39 ICSI procedures for obstructive azoospermia in 24 couples. The
aetiology of the obstruction was failed microsurgery in 11 patients, CBAVD
in nine and genital infections in four. Sperm retrieval was accomplished
via MESA in four cases, PESA in 18 cases and via TESE in 11 cases. TESE was
only applied when PESA failed to produce enough spermatozoa for
simultaneous ICSI. In six patients, the ICSI procedure was performed with
cryopreserved spermatozoa after an initial PESA procedure. Fertilization
occurred in 47% of the metaphase II oocytes; embryo transfer was performed
in 92% of procedures and resulted in a clinical pregnancy in 13/39
procedures. Ongoing pregnancy was achieved in 10/39 procedures. One
pregnancy was terminated early after prenatal investigation showed a
cytogenetic abnormality (47,XX+18, Edwards syndrome). The other nine
pregnancies resulted in the live birth of 10 children, without any
congenital abnormalities. Epididymal and testicular retrieved spermatozoa
were successfully used for ICSI to treat obstructive azoospermia, and
resulted in an ongoing pregnancy in 10 of 24 couples (41.6%) after 39 ICSI
procedures, a success rate of 25.6% per treatment cycle and of 27.7% per
embryo transfer.
相似文献
13.
14.
15.
L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns 总被引:8,自引:3,他引:8
Fransen E; D'Hooge R; Van Camp G; Verhoye M; Sijbers J; Reyniers E; Soriano P; Kamiguchi H; Willemsen R; Koekkoek SK; De Zeeuw CI; De Deyn PP; Van der Linden A; Lemmon V; Kooy RF; Willems PJ 《Human molecular genetics》1998,7(6):999-1009
L1 is a neural cell adhesion molecule mainly involved in axon guidance and
neuronal migration during brain development. Mutations in the human L1 gene
give rise to a complex clinical picture, with mental retardation,
neurologic abnormalities and a variable degree of hydrocephalus. Recently,
a transgenic mouse model with a targeted null mutation in the L1 gene was
generated. These knockout (KO) mice show hypoplasia of the corticospinal
tract. Here we have performed further studies of these KO mice including
magnetic resonance imaging of the brain, neuropathological analysis and
behavioral testing. The ventricular system was shown to be abnormal with
dilatation of the lateral ventricles and the 4th ventricle, and an altered
shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the
KO mice is hypoplastic. Their exploratory behavior is characterized by
stereotype peripheral circling reminiscent of that of rodents with induced
cerebellar lesions.
相似文献
16.
Use of monoclonal antibodies in diagnosis of paracoccidioidomycosis: new strategies for detection of circulating antigens. 总被引:3,自引:3,他引:3
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)
B L Gmez J I Figueroa A J Hamilton B Ortiz M A Robledo R J Hay A Restrepo 《Journal of clinical microbiology》1997,35(12):3278-3283
The precise diagnosis of paracoccidioidomycosis, in most cases, is established by direct methods and indirect immunological tests. The latter method is reliant on the identification of the host's humoral responses, which are usually impaired or absent in patients with severe juvenile forms of the disease and in immunocompromised patients. Determining disease activity or assessing treatment responses by measuring antibody levels is difficult, since antibody titer may remain elevated or persist at stationary levels, even in the presence of clinical improvement. Consequently, there is a need for alternative tests aimed at the identification of circulating antigens. A modification of the standard hybridoma production method was used to raise a panel of murine monoclonal antibodies (MAbs) against the yeast form of Paracoccidioides brasiliensis. Of these, MAb PIB, directed against an 87-kDa determinant, was used to develop an inhibition ELISA (inh-ELISA) capable of detecting as little as 5.8 ng of circulating antigen per ml of serum. Sera from 46 patients with paracoccidioidomycosis or other mycoses and sera from healthy individuals were evaluated by the inh-ELISA; overall sensitivity was 80.4% (37 of 46 paracoccidioidomycosis patients tested positive), and specificity compared with that of normal controls from areas of endemicity was 81.4%. The inh-ELISA detected circulating antigen in 100% of patients with the acute form of paracoccidioidomycosis and in 83.3 and 60% of patients with the chronic multifocal and unifocal forms of paracoccidioidomycosis according to the patients' clinical presentation. These results indicate that the inh-ELISA with MAb PIB is effective in the detection of circulating antigen and that this test may be useful for monitoring responses to treatment and establishing disease prognoses. 相似文献
17.
目的: 研究1,25-二羟维生素D3 对结肠癌细胞系Caco-2 细胞中报告基因表达的作用,并探讨在报告载体pGL2 序列中存在潜在的抑制性维生素D应答元件(VDRE)的可能性。方法: 采用磷酸钙沉淀法将报告载体转染入Caco-2 细胞。Caco-2细胞经不同浓度1,25-二羟维生素D3 处理后测定细胞裂解液中表达的荧光素酶活性。结果: 应用pGL2 报告载体时,当用pSG5-VDR表达载体共转染后,1,25-二羟维生素D3显著地抑制Caco-2 细胞荧光素酶的表达(P< 0.05);而未使用该表达载体共转染则无抑制作用(P> 0.05)。应用pGL3 报告载体时,不同浓度的1,25-二羟维生素D3 对pLG3转染后Caco-2 细胞表达的荧光素酶活性均无显著抑制作用(P> 0.05),该作用不依赖是否存在有pSG5-VDR表达载体共转染。结论:1,25-二羟维生素D3 对报告载体PGL2 荧光素酶表达具有抑制作用,而对pGL3 则否;类似人类PTH基因中的潜在抑制性VDRE存在于报告载体pGL2,在pGL3 中该VDRE业已改变。 相似文献
18.
Kimberly E. Vanover Silvia Robledo Matthew Huber Richard B. Carter 《Psychopharmacology》1999,145(3):333-341
Rationale: Conflict procedures used to detect anxiolytic-like activity of drugs often rely on maintaining strict schedules of water
or food availability. It is ethically and practically desirable to reduce such states of deprivation in animal testing. Objective: The purpose of the present experiment was to develop and pharmacologically characterize a conflict drinking procedure that
did not require the use of water-deprived animals. Methods: Rats were tested during daily sessions with alternating unpunished drinking (no tone: lick=sucrose solution) and signaled
punished drinking (tone: lick=sucrose+shock) components, and developed individual steady baselines over a brief training period
(approximately 3–4 weeks). The drugs tested i.p. were the positive allosteric modulators of γ-amino butyric acidA (GABA)A receptors, diazepam (0.03–30 mg/kg), chlordiazepoxide (0.03–30 mg/kg), lorazepam (0.03–10 mg/kg), zolpidem (0.3–10 mg/kg),
pentobarbital (1–30 mg/kg), pregnanolone (1–30 mg/kg), and bretazenil (0.03– 10 mg/kg); the 5-hydroxy tryptamine1A (HT)1A-mediated anxiolytics, buspirone (1–10 mg/kg) and ipsapirone (1–17 mg/kg); and the negative controls d-amphetamine (0.3–3 mg/kg), haloperidol (0.01–0.3 mg/kg), morphine (0.3–17 mg/kg), and imipramine (0.3–30 mg/kg). Results: The experimental procedure was sensitive to increases in punished drinking by the GABAA-positive modulators, consistent with their known or putative anxiolytic activity. Further, the 5-HT1A-mediated anxiolytics increased punished drinking, although to a lesser extent and over a more narrow dose range than did
the GABAergic drugs. In contrast, d-amphetamine, haloperidol, morphine, and imipramine failed to increase punished drinking up to doses that decreased unpunished
drinking. Conclusions: The present results indicate that water deprivation is not a necessary condition to engender drinking conflict behavior or
to obtain pharmacological effects similar to those obtained with other classical conflict procedures.
Received: 23 November 1998 / Final version: 15 March 1999 相似文献
19.
20.
Expression profiling of T-cell lymphomas differentiates peripheral and lymphoblastic lymphomas and defines survival related genes. 总被引:1,自引:0,他引:1
Beatriz Martinez-Delgado Barbara Meléndez Marta Cuadros Javier Alvarez Jose Maria Castrillo Ana Ruiz De La Parte Manuela Mollejo Carmen Bellas Ramon Diaz Luis Lombardía Fatima Al-Shahrour Orlando Domínguez Alberto Cascon Mercedes Robledo Carmen Rivas Javier Benitez 《Clinical cancer research》2004,10(15):4971-4982
PURPOSE: T-Cell lymphomas constitute heterogeneous and aggressive tumors in which pathogenic alterations remain largely unknown. Expression profiling has demonstrated to be a useful tool for molecular classification of tumors. EXPERIMENTAL DESIGN: Using DNA microarrays (CNIO-OncoChip) containing 6386 cancer-related genes, we established the expression profiling of T-cell lymphomas and compared them to normal lymphocytes and lymph nodes. RESULTS: We found significant differences between the peripheral and lymphoblastic T-cell lymphomas, which include a deregulation of nuclear factor-kappaB signaling pathway. We also identify differentially expressed genes between peripheral T-cell lymphoma tumors and normal T lymphocytes or reactive lymph nodes, which could represent candidate tumor markers of these lymphomas. Additionally, a close relationship between genes associated to survival and those that differentiate among the stages of disease and responses to therapy was found. CONCLUSIONS: Our results reflect the value of gene expression profiling to gain insight about the molecular alterations involved in the pathogenesis of T-cell lymphomas. 相似文献