首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   1147篇
  免费   77篇
  国内免费   1篇
  1225篇
  2023年   14篇
  2022年   33篇
  2021年   35篇
  2020年   13篇
  2019年   22篇
  2018年   25篇
  2017年   22篇
  2016年   34篇
  2015年   65篇
  2014年   58篇
  2013年   95篇
  2012年   82篇
  2011年   110篇
  2010年   33篇
  2009年   52篇
  2008年   54篇
  2007年   45篇
  2006年   51篇
  2005年   30篇
  2004年   50篇
  2003年   23篇
  2002年   30篇
  2001年   22篇
  2000年   33篇
  1999年   21篇
  1998年   10篇
  1997年   3篇
  1996年   3篇
  1995年   3篇
  1994年   4篇
  1993年   7篇
  1992年   11篇
  1991年   14篇
  1990年   14篇
  1989年   10篇
  1988年   12篇
  1987年   11篇
  1985年   7篇
  1984年   10篇
  1983年   8篇
  1982年   7篇
  1981年   6篇
  1979年   4篇
  1978年   3篇
  1977年   3篇
  1976年   3篇
  1974年   3篇
  1971年   2篇
  1970年   2篇
  1969年   3篇
排序方式: 共有1225条查询结果,搜索用时 15 毫秒
991.

Background

Risk behaviors among female sex workers (FSW) are considerable drivers of HIV infections in Vietnam, especially transmission between high-risk and low-risk groups. We assessed HIV prevalence and its correlates among FSWs, and the use of preventive services among this community in the Mekong Delta region, southern Vietnam.

Methods

A cross-sectional survey of 1,999 FSWs was carried out in five provinces including Ben Tre, Hau Giang, Kien Giang, Tien Giang, and Vinh Long between June, 2006 and June, 2007. We interviewed participants face-to-face in order to elicit information about their lives and potential risk factors, and we tested their sera to determine their HIV status. We then performed multivariate logistic regression analyses to investigate factors associated with HIV infection.

Results

Seventeen percent of the participating FSWs were street-based sex workers (SSWs) and the rest (83%) were entertainment establishment-based sex workers (ESWs). Unprotected sex with regular and casual clients in the past month was frequent among study participants (40.5% and 33.5% respectively). However, few respondents (1.3%) had ever injected drugs. Only 2.1% (95% confidence interval (CI): 1.6%–2.8%) of FSWs were found to be infected with HIV. HIV prevalence among SSWs was greater than among ESWs (3.8% vs. 1.8%, p = 0.02, respectively). Increased risk for HIV infection was significantly associated with the number of clients per month (adjusted odd ratio (aOR) = 2.65, 95% CI: 1.26–5.59).

Conclusions

Interventions to reduce unsafe sex and drug injection, and to increase uptake of HIV testing among FSWs are necessary. Differences in HIV prevalence and its correlates by type of sex work emphasize the importance of constrained contexts in shaping risk behaviors among FSWs; that should be considered in designing HIV prevention programs.  相似文献   
992.
A new deletion allele of the APETALA1 (AP1) gene encoding a type II MADS-box protein with the key role in the initiation of flowering and development of perianth organs has been identified in A. thaliana. The deletion of seven amino acids in the conserved region of the K domain in the ap1-20 mutant considerably delayed flowering and led to a less pronounced abnormality in the corolla development compared to the weak ap1-3 and intermediate ap1-6 alleles. At the same time, a considerable stamen reduction has been revealed in ap1-20 as distinct from ap1-3 and ap1-6 alleles. These data indicate that the K domain of AP1 can be crucial for the initiation of flowering and expression regulation of B-class genes controlling stamen development.  相似文献   
993.
994.
Human leukemia inhibitory factor (hLIF) is a multifunctional cytokine that is essential for maintaining the pluripotency of embryonic stem cells. hLIF may be also be useful in aiding fertility through its effects on increasing the implantation rate of fertilized eggs. Thus these applications in biomedical research and clinical medicine create a high demand for bioactive hLIF. However, production of active hLIF is problematic since eukaryotic cells demonstrate limited expression and prokaryotic cells produce insoluble protein. Here, we have adopted a hybrid protein disulfide isomerase design to increase the solubility of hLIF in Escherichia coli. Low temperature expression of hLIF fused to the b''a'' domain of protein disulfide isomerase (PDIb''a'') increased the soluble expression in comparison to controls. A simple purification protocol for bioactive hLIF was established that includes removal of the PDIb''a'' domain by cleavage by TEV protease. The resulting hLIF, which contains one extra glycine residue at the N-terminus, was highly pure and demonstrated endotoxin levels below 0.05 EU/μg. The presence of an intramolecular disulfide bond was identified using mass spectroscopy. This purified hLIF effectively maintained the pluripotency of a murine embryonic stem cell line. Thus we have developed an effective method to produce a pure bioactive version of hLIF in E. coli for use in biomedical research.  相似文献   
995.

Introduction

Face-to-face (FTF) interviews are the most frequently used means of obtaining information on sexual and drug injecting behaviours from men who have sex with men (MSM) and men who inject drugs (MWID). However, accurate information on these behaviours may be difficult to elicit because of sociocultural hostility towards these populations and the criminalization associated with these behaviours. Audio computer assisted self-interview (ACASI) is an interviewing technique that may mitigate social desirability bias in this context.

Methods

This study evaluated differences in the reporting of HIV-related risky behaviours by MSM and MWID using ACASI and FTF interviews. Between August and September 2010, 712 MSM and 328 MWID in Nigeria were randomized to either ACASI or FTF interview for completion of a behavioural survey that included questions on sensitive sexual and injecting risk behaviours. Data were analyzed separately for MSM and MWID. Logistic regression was run for each behaviour as a dependent variable to determine differences in reporting methods.

Results

MSM interviewed via ACASI reported significantly higher risky behaviours with both women (multiple female sexual partners 51% vs. 43%, p = 0.04; had unprotected anal sex with women 72% vs. 57%, p = 0.05) and men (multiple male sex partners 70% vs. 54%, p≤0.001) than through FTF. Additionally, they were more likely to self-identify as homosexual (AOR: 3.3, 95%CI:2.4–4.6) and report drug use in the past 12 months (AOR:40.0, 95%CI: 9.6–166.0). MWID interviewed with ACASI were more likely to report needle sharing (AOR:3.3, 95%CI:1.2–8.9) and re-use (AOR:2.2, 95%CI:1.2–3.9) in the past month and prior HIV testing (AOR:1.6, 95%CI 1.02–2.5).

Conclusion

The feasibility of using ACASI in studies and clinics targeting key populations in Nigeria must be explored to increase the likelihood of obtaining more accurate data on high risk behaviours to inform improved risk reduction strategies that reduce HIV transmission.  相似文献   
996.
In Vitro Cellular & Developmental Biology - Plant - Isoflavones, which are secondary metabolites synthesised through the phenylpropanoid pathway, play important roles in many essential...  相似文献   
997.
Structural results with minor groove binding agents, such as netropsin, have provided detailed, atomic level views of DNA molecular recognition. Solution studies, however, indicate that there is complexity in the binding of minor groove agents to a single site. Netropsin, for example, has two DNA binding enthalpies in isothermal titration calorimetry (ITC) experiments that indicate the compound simultaneously forms two thermodynamically different complexes at a single AATT site. Two proposals for the origin of this unusual observation have been developed: (i) two different bound species of netropsin at single binding sites and (ii) a netropsin induced DNA hairpin to duplex transition. To develop a better understanding of DNA recognition complexity, the two proposals have been tested with several DNAs and the methods of mass spectrometry (MS), polyacrylamide gel electrophoresis (PAGE) and nuclear magnetic resonance spectroscopy in addition to ITC. All of the methods with all of the DNAs investigated clearly shows that netropsin forms two different complexes at AATT sites, and that the proposal for an induced hairpin to duplex transition in this system is incorrect.  相似文献   
998.
999.
Previous efforts towards S. aureus vaccine development have largely focused on cell surface antigens to induce opsonophagocytic killing aimed at providing sterile immunity, a concept successfully applied to other Gram-positive pathogens such as Streptococcus pneumoniae. However, these approaches have largely failed, possibly in part due to the remarkable diversity of the staphylococcal virulence factors such as secreted immunosuppressive and tissue destructive toxins. S. aureus produces several pore-forming toxins including the single subunit alpha hemolysin as well as bicomponent leukotoxins such as Panton-Valentine leukocidin (PVL), gamma hemolysins (Hlg), and LukED. Here we report the generation of highly attenuated mutants of PVL subunits LukS-PV and LukF-PV that were rationally designed, based on an octameric structural model of the toxin, to be deficient in oligomerization. The attenuated subunit vaccines were highly immunogenic and showed significant protection in a mouse model of S. aureus USA300 sepsis. Protection against sepsis was also demonstrated by passive transfer of rabbit immunoglobulin raised against LukS-PV. Antibodies to LukS-PV inhibited the homologous oligomerization of LukS-PV with LukF-PV as well heterologous oligomerization with HlgB. Importantly, immune sera from mice vaccinated with the LukS mutant not only inhibited the PMN lytic activity produced by the PVL-positive USA300 but also blocked PMN lysis induced by supernatants of PVL-negative strains suggesting a broad protective activity towards other bicomponent toxins. These findings strongly support the novel concept of an anti-virulence, toxin-based vaccine intended for prevention of clinical S. aureus invasive disease, rather than achieving sterile immunity. Such a multivalent vaccine may include attenuated leukotoxins, alpha hemolysin, and superantigens.  相似文献   
1000.

Background

The pathogenesis of acute measles encephalitis (AME) is poorly understood. Treatment with immune-modulators is based on theories that post-infectious autoimmune responses cause demyelination. The clinical course and immunological parameters of AME were examined during an outbreak in Vietnam.

Methods and Findings

Fifteen measles IgM-positive patients with confusion or Glasgow Coma Scale (GCS) score below 13, and thirteen with uncomplicated measles were enrolled from 2008–2010. Standardized clinical exams were performed and blood collected for lymphocyte and measles- and auto-antibody analysis. The median age of AME patients was 21 years, similar to controls. Eleven reported receiving measles vaccination when aged one year. Confusion developed a median of 4 days after rash. Six patients had GCS <8 and four required mechanical ventilation. CSF showed pleocytosis (64%) and proteinorrhachia (71%) but measles virus RNA was not detected. MRI revealed bilateral lesions in the cerebellum and brain stem in some patients. Most received dexamethasone +/− IVIG within 4 days of admission but symptoms persisted for ≥3 weeks in five. The concentration of voltage gated calcium channel-complex-reactive antibodies was 900 pM in one patient, and declined to 609 pM ∼ 3 months later. Measles-reactive IgG antibody avidity was high in AME patients born after vaccine coverage exceeded 50% (∼ 25 years earlier). AME patients had low CD4 (218/µl, p = 0.029) and CD8 (200/µl, p = 0.012) T-cell counts compared to controls.

Conclusion

Young adults presenting with AME in Vietnam reported a history of one prior measles immunization, and those aged <25 years had high measles-reactive IgG avidity indicative of prior vaccination. This suggests that one-dose measles immunization is not sufficient to prevent AME in young adults and reinforces the importance of maintaining high coverage with a two-dose measles immunization schedule. Treatment with corticosteroids and IVIG is common practice, and should be assessed in randomized clinical trials.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号