全文获取类型
收费全文 | 5937篇 |
免费 | 519篇 |
国内免费 | 3篇 |
出版年
2023年 | 42篇 |
2022年 | 116篇 |
2021年 | 222篇 |
2020年 | 93篇 |
2019年 | 128篇 |
2018年 | 145篇 |
2017年 | 104篇 |
2016年 | 210篇 |
2015年 | 365篇 |
2014年 | 331篇 |
2013年 | 407篇 |
2012年 | 569篇 |
2011年 | 499篇 |
2010年 | 317篇 |
2009年 | 241篇 |
2008年 | 351篇 |
2007年 | 359篇 |
2006年 | 317篇 |
2005年 | 283篇 |
2004年 | 285篇 |
2003年 | 234篇 |
2002年 | 215篇 |
2001年 | 45篇 |
2000年 | 28篇 |
1999年 | 38篇 |
1998年 | 57篇 |
1997年 | 28篇 |
1996年 | 27篇 |
1995年 | 19篇 |
1994年 | 31篇 |
1993年 | 29篇 |
1992年 | 19篇 |
1991年 | 20篇 |
1990年 | 15篇 |
1989年 | 16篇 |
1988年 | 12篇 |
1987年 | 9篇 |
1986年 | 10篇 |
1985年 | 14篇 |
1984年 | 18篇 |
1983年 | 15篇 |
1982年 | 14篇 |
1981年 | 8篇 |
1980年 | 13篇 |
1979年 | 7篇 |
1978年 | 13篇 |
1977年 | 11篇 |
1976年 | 8篇 |
1975年 | 7篇 |
1971年 | 11篇 |
排序方式: 共有6459条查询结果,搜索用时 125 毫秒
121.
Aaron R. Everitt Simon Clare Jacqueline U. McDonald Leanne Kane Katherine Harcourt Malika Ahras Amar Lall Christine Hale Angela Rodgers Douglas B. Young Ashraful Haque Oliver Billker John S. Tregoning Gordon Dougan Paul Kellam 《PloS one》2013,8(11)
The interferon-inducible transmembrane (IFITM) family of proteins has been shown to restrict a broad range of viruses in vitro and in vivo by halting progress through the late endosomal pathway. Further, single nucleotide polymorphisms (SNPs) in its sequence have been linked with risk of developing severe influenza virus infections in humans. The number of viruses restricted by this host protein has continued to grow since it was first demonstrated as playing an antiviral role; all of which enter cells via the endosomal pathway. We therefore sought to test the limits of antimicrobial restriction by Ifitm3 using a knockout mouse model. We showed that Ifitm3 does not impact on the restriction or pathogenesis of bacterial (Salmonella typhimurium, Citrobacter rodentium, Mycobacterium tuberculosis) or protozoan (Plasmodium berghei) pathogens, despite in vitro evidence. However, Ifitm3 is capable of restricting respiratory syncytial virus (RSV) in vivo either through directly restricting RSV cell infection, or by exerting a previously uncharacterised function controlling disease pathogenesis. This represents the first demonstration of a virus that enters directly through the plasma membrane, without the need for the endosomal pathway, being restricted by the IFITM family; therefore further defining the role of these antiviral proteins. 相似文献
122.
Magelda Montoya Lionel Gresh Juan Carlos Mercado Katherine L. Williams Maria José Vargas Gamaliel Gutierrez Guillermina Kuan Aubree Gordon Angel Balmaseda Eva Harris 《PLoS neglected tropical diseases》2013,7(8)
Four dengue virus serotypes (DENV1-4) circulate globally, causing more human illness than any other arthropod-borne virus. Dengue can present as a range of clinical manifestations from undifferentiated fever to Dengue Fever to severe, life-threatening syndromes. However, most DENV infections are inapparent. Yet, little is known about determinants of inapparent versus symptomatic DENV infection outcome. Here, we analyzed over 2,000 DENV infections from 2004 to 2011 in a prospective pediatric cohort study in Managua, Nicaragua. Symptomatic cases were captured at the study health center, and paired healthy annual samples were examined on a yearly basis using serological methods to identify inapparent DENV infections. Overall, inapparent and symptomatic DENV infections were equally distributed by sex. The mean age of infection was 1.2 years higher for symptomatic DENV infections as compared to inapparent infections. Although inapparent versus symptomatic outcome did not differ by infection number (first, second or third/post-second DENV infections), substantial variation in the proportion of symptomatic DENV infections among all DENV infections was observed across study years. In participants with repeat DENV infections, the time interval between a first inapparent DENV infection and a second inapparent infection was significantly shorter than the interval between a first inapparent and a second symptomatic infection. This difference was not observed in subsequent infections. This result was confirmed using two different serological techniques that measure total anti-DENV antibodies and serotype-specific neutralizing antibodies, respectively. Taken together, these findings show that, in this study, age, study year and time interval between consecutive DENV infections influence inapparent versus symptomatic infection outcome, while sex and infection number had no significant effect. Moreover, these results suggest that the window of cross-protection induced by a first infection with DENV against a second symptomatic infection is approximately 2 years. These findings are important for modeling dengue epidemics and development of vaccines. 相似文献
123.
124.
Rapeephan R. Maude Md Amir Hossain Mahtab Uddin Hassan Sophie Osbourne Katherine Langan Abu Sayeed Mohammed Rezaul Karim Rasheda Samad Shyamanga Borooah Bal Dhillon Nicholas P. J. Day Arjen M. Dondorp Richard J. Maude 《PloS one》2013,8(12)
Introduction
Measurement of optic nerve sheath diameter (ONSD) by ultrasound is increasingly used as a marker to detect raised intracranial pressure (ICP). ONSD varies with age and there is no clear consensus between studies for an upper limit of normal. Knowledge of normal ONSD in a healthy population is essential to interpret this measurement.Methods
In a prospective observational study, ONSD was measured using a 15 MHz ultrasound probe in healthy volunteers in Chittagong, Bangladesh. The aims were to determine the normal range of ONSD in healthy Bangladeshi adults and children, compare measurements in males and females, horizontal and vertical beam orientations and left and right eyes in the same individual and to determine whether ONSD varies with head circumference independent of age.Results
136 subjects were enrolled, 12.5% of whom were age 16 or under. Median ONSD was 4.41 mm with 95% of subjects in the range 4.25–4.75 mm. ONSD was bimodally distributed. There was no relationship between ONSD and age (≥4 years), gender, head circumference, and no difference in left vs right eye or horizontal vs vertical beam.Conclusions
Ultrasonographic ONSD in Bangladeshi healthy volunteers has a narrow bimodal distribution independent of age (≥4 years), gender and head circumference. ONSD >4.75 mm in this population should be considered abnormal. 相似文献125.
126.
Katherine J. Nicholas Emily K. Zern Louise Barnett Rita M. Smith Shelly L. Lorey Courtney A. Copeland Shanmugalakshmi Sadagopal Spyros A. Kalams 《PloS one》2013,8(12)
Infection with Human Immunodeficiency Virus Type 1 (HIV-1) induces defects of both cellular and humoral immune responses. Impaired CD4+ T cell help and B cell dysfunction may partially explain the low frequency of broadly neutralizing antibodies in HIV-infected individuals. To understand the extent of B cell dysfunction during HIV infection, we assessed the level of B cell activation at baseline and after stimulation with a variety of antigens. Increased levels of viremia were associated with higher baseline expression of the activation marker CD86 on B cells and with decreased ability of B cells to increase expression of CD86 after in vitro stimulation with inactivated HIV-1. In a series of cell isolation experiments B cell responses to antigen were enhanced in the presence of autologous CD4+ T cells. HIV infected individuals had a higher frequency of PD-1 expression on B cells compared to HIV- subjects and PD-1 blockade improved B cell responsiveness to HIV antigen, suggesting that inhibitory molecule expression during HIV-1 infection may contribute to some of the observed B cell defects. Our findings demonstrate that during chronic HIV infection, B cells are activated and lose full capacity to respond to antigen, but suppression of inhibitory pressures as well as a robust CD4+ T cell response may help preserve B cell function. 相似文献
127.
128.
Katherine R. Bull Andrew J. Rimmer Owen M. Siggs Lisa A. Miosge Carla M. Roots Anselm Enders Edward M. Bertram Tanya L. Crockford Belinda Whittle Paul K. Potter Michelle M. Simon Ann-Marie Mallon Steve D. M. Brown Bruce Beutler Christopher C. Goodnow Gerton Lunter Richard J. Cornall 《PLoS genetics》2013,9(1)
Forward genetics screens with N-ethyl-N-nitrosourea (ENU) provide a powerful way to illuminate gene function and generate mouse models of human disease; however, the identification of causative mutations remains a limiting step. Current strategies depend on conventional mapping, so the propagation of affected mice requires non-lethal screens; accurate tracking of phenotypes through pedigrees is complex and uncertain; out-crossing can introduce unexpected modifiers; and Sanger sequencing of candidate genes is inefficient. Here we show how these problems can be efficiently overcome using whole-genome sequencing (WGS) to detect the ENU mutations and then identify regions that are identical by descent (IBD) in multiple affected mice. In this strategy, we use a modification of the Lander-Green algorithm to isolate causative recessive and dominant mutations, even at low coverage, on a pure strain background. Analysis of the IBD regions also allows us to calculate the ENU mutation rate (1.54 mutations per Mb) and to model future strategies for genetic screens in mice. The introduction of this approach will accelerate the discovery of causal variants, permit broader and more informative lethal screens to be used, reduce animal costs, and herald a new era for ENU mutagenesis. 相似文献
129.
130.
Brian C. Geyer Katherine E. Larrimore Jacquelyn Kilbourne Latha Kannan Tsafrir S. Mor 《PloS one》2013,8(3)