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1.
Practical management of patients with non-small-cell lung cancer treated with gefitinib. 总被引:7,自引:0,他引:7
Neelam T Shah Mark G Kris William Pao Leslie B Tyson Barbara M Pizzo Murk-Hein Heinemann Leah Ben-Porat Dana L Sachs Robert T Heelan Vincent A Miller 《Journal of clinical oncology》2005,23(1):165-174
PURPOSE: The use of gefitinib, the first drug approved to inhibit the epidermal growth factor receptor tyrosine kinase, is indicated in patients with non-small-cell lung cancer with tumors progressive after chemotherapy. The unique mechanism of action of this agent leads to distinctive patterns of response and toxicity in persons with lung cancer. Many of the principles of management relevant to gefitinib are distinct from those with conventional cytotoxic drugs. To meet this need, we present practical guidelines on the use of gefitinib in patients with non-small-cell lung cancer. METHODS: This article reviews gefitinib's indications, dosing, response phenomena, and patterns of relapse in individuals with radiographic response. RESULTS: We present our recommendations for the management of rash and diarrhea caused by this agent. CONCLUSION: This information can guide practitioners and help them inform their patients about what to expect when they receive gefitinib. 相似文献
2.
The in vitro DNA amplification technique of polymerase chain reaction was used to evaluate the possible presence of human papillomavirus (HPV) in small cell carcinoma of the uterine cervix. None of the 12 cases examined contain detectable amounts of either HPV type 16, 18, 31, or 33 DNA. On the other hand, HPV types 16 and 18 DNA were found in 14 (93.3%) and 9 (60.0%) of 25 invasive cervical squamous carcinoma tissues. The results seem to suggest that these types of HPV are not present or are present in extremely small quantities in cervical small cell carcinoma. Such an absence of HPV DNA makes it unlikely that these types of HPV play any etiological role in the pathogenesis of cervical small cell carcinoma. 相似文献
3.
Distribution of, and immune response to, chicken anti-alpha Gal immunoglobulin Y antibodies in wild-type and alpha Gal knockout mice 下载免费PDF全文
Walsh WE Anderson BE Ivancic D Zhang Z Piccini JP Rodgers TG Pao W Fryer JP 《Immunology》2000,101(4):467-473
Chicken antibodies (immunoglobulin Y; IgY) to the alpha Gal epitope (galactose alpha-1,3-galactose) bind to alpha Gal antigens of mouse and porcine tissues and endothelial cells in vitro and block human anti-alpha Gal antibody binding, complement activation and antibody-dependent cell-mediated lysis mechanisms. The activities and toxicity of anti-alpha Gal IgY have not been tested in vivo. In this study, we tested the effects of multiple injections of affinity-purified anti-alpha Gal IgY (AP-IgY) in both wild-type (WT) and alpha-1,3-galactosyltransferase knockout (Gal KO) mice. WT and Gal KO mice were injected once, twice, three, or four times intravenously (i.v.) with AP-IgY and killed at 1 hr or 24 hr. Mice displayed no toxicity to four injections of AP-IgY. Heart, lung, liver, kidney, spleen and pancreatic tissue were evaluated using immunohistochemical techniques for the presence of the alpha Gal epitope using the GSI-B4 lectin, and for bound IgY, as well as mouse IgM and IgG. The binding of AP-IgY antibodies to the endothelium of WT mouse tissues was essentially identical to the pattern of binding of the GSI-B4 lectin after injection of WT mice and death at 1 hr. WT mice killed 24 hr after i.v. injection of AP-IgY showed little remaining bound IgY in their endothelia, indicating that IgY is cleared over that time period. We also evaluated the blood drawn at the time of death for the presence of anti-alpha Gal IgY, anti-IgY IgM and anti-IgY IgG by enzyme-linked immunosorbent assay. Anti-alpha Gal IgY was almost undetectable in WT mouse sera at all injection and killing times. In contrast, Gal KO mouse sera showed increasing anti-alpha Gal IgY levels until 24 hr after the fourth injection, when anti-alpha Gal IgY levels were almost undetectable. Anti-IgY IgM and IgG levels in WT and Gal KO mouse sera showed a typical increase in anti-IgY IgM 24 hr after the second injection (3 days after the first injection) and an increase in anti-IgY IgG 24 hr after the third injection (5 days after the first injection). These results show that IgY binds to alpha Gal epitopes in the WT mice and is cleared sometime over a 24-hr time period and that IgY is an expected immunogen in mice eliciting a rather typical anti-IgY IgM and IgG response. 相似文献
4.
Lee Dianda Adam Gulbranson-Judge William Pao Adrian C. Hayday Ian C. M. Maclennan Michael J. Owen 《European journal of immunology》1996,26(7):1603-1607
T cells are essential for inducing clonal B cell expansion in germinal centers during T cell-dependent antibody responses. However, class-switched antibodies are readily detectable in TCRα-deficient mice that congenitally lack αβ T cells, including those such as IgG1 that are considered to be dependent on collaboration between B cells and αβ T cells. This observation suggests that a novel form of B:T collaboration may be evident in TCRα?/? mice. We report that germinal centers develop spontaneously in mice lacking T cell receptor α genes (TCRα?/?), despite the absence of αβ T cells. They are not seen in TCRβ?/? mice kept in similar conditions. Both strains of mice have γδ T cells, but it is a subset of T cells expressing TCRβ and CD4 that is dominant in the germinal centers of TCRα?/? mice. Exceptionally, germinal centers were associated with CD4+ γδ T cells. The expression of CD4 seems to be important, for few extrafollicular T cells have CD4 and CD4 is largely absent from TCRβ?/? T cells. The CD4+ TCRβ cells may help B cells produce autoantibodies that have been identified in TCRα?/? mice. 相似文献
5.
Idiopathic arterial calcification of infancy is a rare condition characterized by extensive arterial calcification and stenoses
of large and medium sized arteries. We report the sonographic and magnetic resonance angiographic findings of this entity
and correlate them with the findings at autopsy.
Received: 20 October 1997 Accepted: 21 November 1997 相似文献
6.
OBJECTIVE: To our knowledge, this article is the first to describe a series of patients with avulsion fractures of the base of the fifth metatarsal that were not seen on conventional radiography using the standard three views of the foot but that were seen on radiography of the ankle. CONCLUSION: Because routine radiographs of the foot may fail to reveal an avulsion fracture of the base of the fifth metatarsal, an additional projection should be obtained to better assess this region in the symptomatic patient. The additional view should be an anteroposterior radiograph of the ankle that includes the base of the fifth metatarsal because this projection has been shown to help in the diagnosis of this avulsion fracture. 相似文献
7.
8.
Ivan Vujkovic-Cvijin Rachel L. Rutishauser Montha Pao Peter W. Hunt Susan V. Lynch Joseph M. McCune 《Gut microbes》2017,8(5):440-450
Many HIV-infected individuals on antiretroviral therapy (ART) exhibit persistent systemic inflammation, which predicts morbidity and mortality. ART-treated subjects concurrently exhibit marked compositional alterations in the gut bacterial microbiota and the degree of dysbiosis correlates with systemic inflammation. Whether interventions to modulate the microbiome can affect systemic inflammation is unknown. An open-label fecal microbial transplantation (FMT) was delivered by colonoscopy to asymptomatic HIV-infected ART-suppressed individuals without antibiotic pre-treatment. Stool was assessed before and after FMT for engraftment of donor microbes, and peripheral blood was assayed for immune activation biomarkers. Six participants received FMT and 2 participants served as controls. No serious adverse effects occurred during 24 weeks of follow-up. At baseline, HIV-infected individuals exhibited microbiota profiles distinct from uninfected donors. During the 8 weeks post-FMT, recipients demonstrated partial engraftment of the donor microbiome (P < 0.05). Recipient microbiota remained significantly distant from donors, unlike that observed following FMT for treatment of C. difficile infection. Systemic inflammatory markers showed no significant change post-FMT. FMT was well-tolerated in ART-treated, HIV-infected individuals. Engraftment was detectable but modest, and appeared to be limited to specific bacterial taxa. Whether antibiotic conditioning can enhance engraftment and the capacity of microbiota to modulate inflammation remains to be investigated. 相似文献
9.
Responses of glutathione‐related antioxidant defense system in serum of Nile tilapia (Oreochromis niloticus) exposed to sublethal concentration of methomyl and recovery pattern 下载免费PDF全文
Shun‐Long Meng Jian‐Hong Qu Li‐Min Fan Li‐Ping Qiu Jia‐Zhang Chen Pao Xu 《Environmental toxicology》2015,30(4):483-489
Tilapia were exposed to sublethal concentrations of 0, 0.2, 2, 20, or 200 μg/L for 30 days, and then transferred to methomyl‐free water for 18 days. GST, GPx, GR, GSH, and GSSG in tilapia serum were examined at 0, 6, 12, 18, 24, and 30 days after methomyl exposure and at 18 days after transferring to methomyl‐free water. There were no significant changes in antioxidants activities and contents in serum of tilapia exposed to 0.2 μg/L. Significant increases in GST, GR, GPx, and GSSG accompanied by a decrease in GSH were observed following methomyl exposure to 2, 20, or 200 μg/L, suggesting the presence of oxidative stress. Thus, it would appear the 0.2 μg/L methomyl might be considered the no observed adverse effect level. Recovery data showed that the effects produced by lower concentration of 20 μg/L were reversible but not at the higher 200 μg/L concentration. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 483–489, 2015. 相似文献
10.
Pownall HJ Brauchi D Kilinç C Osmundsen K Pao Q Payton-Ross C Gotto AM Ballantyne CM 《Atherosclerosis》1999,143(2):285-297
Serum triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations are inversely correlated and mechanistically linked by means of lipid transfer activities. Phospholipid transfer activity (PLTA) moves phospholipids among serum lipoproteins; cholesteryl ester transfer activity (CETA), which exchanges cholesteryl esters (CE) and TG among lipoproteins, is stimulated by nonesterified fatty acids (NEFA). The aims of this study were (a) to develop a quantitative model that correlates the neutral lipid (NL = CE + TG) compositions of HDL and LDL with serum TG concentration; (b) identify the serum lipid determinants of CETA and PLTA, and; (c) identify the effects of serum TG reductions on the neutral lipid compositions of HDL and LDL, serum NEFA concentrations, and on PLTA and CETA. These aims were addressed in 40 hypertriglyceridemic subjects before and after treatment with an 85% concentrate of omega-3 fatty acids (Omacor) and in 16 untreated normolipidemic subjects. In vivo, the NL compositions of LDL and HDL were described by a mathematical model having the form of adsorption isotherms: HDL - (TG/NL) = (0.90 +/- 0.07) serum TG/(7.0 +/- 1.2 mmol/l + serum TG) and LDL - (TG/NL) = (0.65 +/- 0.08) serum TG/(4.9 +/- 1.5 mmol/l + serum TG). Reduction of serum TG was associated with reductions in HDL - (TG/NL), serum NEFA concentration, and serum CETA but not PLTA. These data suggest that both hypertriglyceridemia and the attendant elevated serum CETA but not PLTA are determinants of HDL and LDL composition and structure and that serum TG concentrations are good predictors of the NL compositions of HDL and LDL. 相似文献