全文获取类型
收费全文 | 2291篇 |
免费 | 121篇 |
国内免费 | 76篇 |
专业分类
耳鼻咽喉 | 1篇 |
儿科学 | 172篇 |
妇产科学 | 26篇 |
基础医学 | 292篇 |
口腔科学 | 58篇 |
临床医学 | 297篇 |
内科学 | 644篇 |
皮肤病学 | 75篇 |
神经病学 | 60篇 |
特种医学 | 391篇 |
外科学 | 100篇 |
综合类 | 49篇 |
预防医学 | 98篇 |
眼科学 | 20篇 |
药学 | 92篇 |
2篇 | |
肿瘤学 | 111篇 |
出版年
2023年 | 5篇 |
2022年 | 8篇 |
2021年 | 12篇 |
2020年 | 14篇 |
2019年 | 17篇 |
2018年 | 35篇 |
2017年 | 22篇 |
2016年 | 24篇 |
2015年 | 39篇 |
2014年 | 53篇 |
2013年 | 61篇 |
2012年 | 50篇 |
2011年 | 64篇 |
2010年 | 93篇 |
2009年 | 89篇 |
2008年 | 71篇 |
2007年 | 119篇 |
2006年 | 72篇 |
2005年 | 76篇 |
2004年 | 50篇 |
2003年 | 31篇 |
2002年 | 44篇 |
2001年 | 51篇 |
2000年 | 45篇 |
1999年 | 40篇 |
1998年 | 130篇 |
1997年 | 158篇 |
1996年 | 133篇 |
1995年 | 111篇 |
1994年 | 114篇 |
1993年 | 97篇 |
1992年 | 30篇 |
1991年 | 39篇 |
1990年 | 40篇 |
1989年 | 58篇 |
1988年 | 52篇 |
1987年 | 45篇 |
1986年 | 50篇 |
1985年 | 48篇 |
1984年 | 28篇 |
1983年 | 16篇 |
1982年 | 27篇 |
1981年 | 30篇 |
1980年 | 25篇 |
1979年 | 4篇 |
1978年 | 8篇 |
1977年 | 18篇 |
1976年 | 25篇 |
1975年 | 14篇 |
1966年 | 1篇 |
排序方式: 共有2488条查询结果,搜索用时 0 毫秒
91.
Plana M Garcia F Darwich L Romeu J López A Cabrera C Massanella M Canto E Ruiz-Hernandez R Blanco J Sánchez M Gatell JM Clotet B Ruiz L Bofill M;Red de Investigación en Sida 《Immunology》2011,133(3):318-328
Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. 相似文献
92.
93.
D. Podzamczer J. M Miró E. Ferrer J. M Gatell J. M. Ramón E. Ribera G. Sirera A. Cruceta H. Knobel P. Domingo R. Polo M. Leyes J. Cosin M. C. Fariñas J. Arrizabalaga J. Martínez-Lacasa F. Gudiol 《European journal of clinical microbiology & infectious diseases》2000,19(2):89-95
An open, randomised, multicentre trial was conducted to evaluate the efficacy of thrice-weekly versus daily therapy with
sulfadiazine-pyrimethamine in the prevention of relapses of toxoplasmic encephalitis in HIV-infected patients. Between February
1994 and July 1997, 124 patients with HIV infection were enrolled after resolution of the first acute episode of toxoplasmic
encephalitis treated with sulfadiazine-pyrimethamine. Patients were randomly assigned to receive either a daily regimen consisting
of sulfadiazine (1 g) twice a day plus 25 mg pyrimethamine and 15 mg folinic acid daily (n=58), or a thrice-weekly regimen consisting of the same doses of sulfadiazine and folinic acid plus 50 mg pyrimethamine (n=66). After a median follow-up period of 11 months (range 1–39 months), no differences were found in the incidence of toxoplasmic
encephalitis relapses between the groups, there being 14.9 episodes per 100 patient-years (95% CI: 2.8–20.2) in the daily-regimen
group versus 14.1 episodes (95% CI: 2.3–17.2) in the intermittent-regimen group. The estimated cumulative percentages of relapse
at 12 months were 17% and 19%, respectively (P=0.91). In a Cox multivariate analysis, not taking antiretroviral therapy was the only variable independently associated with
relapse (adjusted risk ratio: 4.08; 95%CI: 1.32–12.66). Baseline CD4+ cell counts, prior AIDS, mental status, sequelae and
allocated maintenance therapy regimen were not independent predictors of relapse. No differences were observed in the survival
rate (P=0.42), or in the incidence of severe adverse effects (P=0.79). The efficacy of the thrice-weekly regimen was similar to that of the daily regimen in the prevention of relapses of
toxoplasmic encephalitis. Administration of antiretroviral therapy was the only factor associated with a lower incidence of
relapse. 相似文献
94.
Paul JM Savelkoul Fabrizio De Mattia Yuedan Li Erik‐Jan Kamsteeg Irene BM Konings Peter van der Sluijs Peter MT Deen 《Human mutation》2009,30(10):E891-E903
Vasopressin regulates human water homeostasis by re‐distributing homotetrameric aquaporin‐2 (AQP2) water channels from intracellular vesicles to the apical membrane of renal principal cells, a process in which phosphorylation of AQP2 at S256 by cAMP‐dependent protein kinase A (PKA) is thought to be essential. Dominant nephrogenic diabetes insipidus (NDI), a disease in which the kidney is unable to concentrate urine in response to vasopressin, is caused by AQP2 gene mutations. Here, we investigated a reported patient case of dominant NDI caused by a novel p.R254Q mutation. Expressed in oocytes, AQP2‐p.R254Q appeared to be a functional water channel, but was impaired in its transport to the cell surface to the same degree as AQP2‐p.S256A, which mimics non‐phosphorylated AQP2. In polarized MDCK cells, AQP2‐p.R254Q was retained and was distributed similarly to that of unstimulated wt‐AQP2 or AQP2‐p.S256A. Upon co‐expression, AQP2‐p.R254Q interacted with, and retained wt‐AQP2 in intracellular vesicles. In contrast to wild‐type AQP2, forskolin did not increase AQP2‐p.R254Q phosphorylation at S256 or its translocation to the apical membrane. Mimicking constitutive phosphorylation in AQP2‐p.R254Q with the p.S256D mutation, however, rescued its apical membrane expression. These date indicate that a lack of S256 phosphorylation is the sole cause of dominant NDI here, and thereby, p.R254Q is a loss of function instead of a gain of function mutation in dominant NDI. © 2009 Wiley‐Liss, Inc. 相似文献
95.
JM Kanyamurwa S Wamala R Baryamutuma E Kabwama R Loewenson 《African health sciences》2013,13(3):829-841
Background
Globalization-related measures to liberalize trade and stimulate export production were applied in Uganda in the late 1980s, including in the coffee production sector, to revitalize agricultural production, increase incomes to farmers and improve rural food security.Objective
To explore the different effects of such measures on the health and dietary outcomes of female coffee and food small holder farmers in Uganda.Methods
We gathered evidence through a cross-sectional comparative interview survey of 190 female coffee producers and 191 female food producers in Ntungamo district. The study mostly employed quantitative methods of data collection, targeting the sampled households. We also utilized qualitative data; collected three months after the household survey data had been collected and their analysis had been accomplished. Using qualitative interviews based on an unstructured interview guide, extra qualitative information was collected from key informants at national, district and community levels. This was among other underlying principles to avoid relying on snapshot information earlier collected at household level in order to draw valid and compelling conclusions from the study. We used indicators of production, income, access to food and dietary patterns, women''s health and health care. Of the two groups selected from the same area, female coffee producers represented a higher level of integration into liberalised export markets.Results
Document review suggests that, although Uganda''s economy grew in the period, the household economic and social gains after the liberalization measures may have been less than expected. In the survey carried out, both food and coffee producers were similarly poor, involved in small-scale production, and of a similar age and education level. Coffee producers had greater land and livestock ownership, greater access to inputs and higher levels of income and used a wider variety of markets than food producers, but they had to work longer hours to obtain these economic returns, and spent more cash on health care and food from commercial sources. Their health outcomes were similar to those of the food producers, but with poorer dietary outcomes and greater food stress.Conclusions
The small-scale women farmers who are producing food cannot rely on the economic infrastructure to give them support for meaningful levels of production. However, despite having higher incomes than their food producing counterparts, the evidence showed that women who are producing coffee in Uganda as an export commodity cannot rely on the income from their crops to guarantee their health and nutritional wellbeing, and that the income advantage gained in coffee-producing households has not translated into consistently better health or food security outcomes. Both groups have limited levels of autonomy and control to address these problems. 相似文献96.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献
97.
98.
JM Hopkin 《Current opinion in immunology》1997,9(6):788-792
Atopy — a T helper 2 cell driven hypersensitivity to innocuous antigens (allergens) which causes most cases of asthma — is of complex genetic and environmental origins. There is compelling epidemiological evidence for a rise in atopic disease in ‘westernised’ communities. The changing pattern of microbial exposure in early childhood is suggested to be the principal candidate mechanism for this rise. 相似文献
99.
Adrian B Levine Jason Peng David Farnell Mitchell Nursey Yiping Wang Julia R Naso Hezhen Ren Hossein Farahani Colin Chen Derek Chiu Aline Talhouk Brandon Sheffield Maziar Riazy Philip P Ip Carlos Parra-Herran Anne Mills Naveena Singh Basile Tessier-Cloutier Taylor Salisbury Jonathan Lee Tim Salcudean Steven JM Jones David G Huntsman C Blake Gilks Stephen Yip Ali Bashashati 《The Journal of pathology》2020,252(2):178-188
Deep learning-based computer vision methods have recently made remarkable breakthroughs in the analysis and classification of cancer pathology images. However, there has been relatively little investigation of the utility of deep neural networks to synthesize medical images. In this study, we evaluated the efficacy of generative adversarial networks to synthesize high-resolution pathology images of 10 histological types of cancer, including five cancer types from The Cancer Genome Atlas and the five major histological subtypes of ovarian carcinoma. The quality of these images was assessed using a comprehensive survey of board-certified pathologists (n = 9) and pathology trainees (n = 6). Our results show that the real and synthetic images are classified by histotype with comparable accuracies and the synthetic images are visually indistinguishable from real images. Furthermore, we trained deep convolutional neural networks to diagnose the different cancer types and determined that the synthetic images perform as well as additional real images when used to supplement a small training set. These findings have important applications in proficiency testing of medical practitioners and quality assurance in clinical laboratories. Furthermore, training of computer-aided diagnostic systems can benefit from synthetic images where labeled datasets are limited (e.g. rare cancers). We have created a publicly available website where clinicians and researchers can attempt questions from the image survey ( http://gan.aimlab.ca/ ). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
100.
Hendrik Wermann Hans Stoop Ad JM Gillis Friedemann Honecker Ruud JHLM van Gurp Ole Ammerpohl Julia Richter J Wolter Oosterhuis Carsten Bokemeyer Leendert HJ Looijenga 《The Journal of pathology》2010,221(4):433-442
Differences in the global methylation pattern, ie hyper‐ as well as hypo‐methylation, are observed in cancers including germ cell tumours (GCTs). Related to their precursor cells, GCT methylation status differs according to histology. We investigated the methylation pattern of normal fetal, infantile, and adult germ cells (n = 103) and GCTs (n = 251) by immunohistochemical staining for 5‐ cytidine. The global methylation pattern of male germ cells changes from hypomethylation to hypermethylation, whereas female germ cells remain unmethylated at all stages. Undifferentiated GCTs (seminomas, intratubular germ cell neoplasia unclassified, and gonadoblastomas) are hypomethylated, whereas more differentiated GCTs (teratomas, yolk sac tumours, and choriocarcinomas) show a higher degree of methylation. Embryonal carcinomas show an intermediate pattern. Resistance to cisplatin was assessed in the seminomatous cell line TCam‐2 before and after demethylation using 5‐azacytidine. Exposure to 5‐azacytidine resulted in decreased resistance to cisplatin. Furthermore, after demethylation, the stem cell markers NANOG and POU5F1 (OCT3/4), as well as the germ cell‐specific marker VASA, showed increased expression. Following treatment with 5‐azacytidine, TCam‐2 cells were analysed using a high‐throughput methylation screen for changes in the methylation sites of 14 000 genes. Among the genes revealing changes, interesting targets were identified: ie demethylation of KLF11, a putative tumour suppressor gene, and hypermethylation of CFLAR, a gene previously described in treatment resistance in GCTs. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献