全文获取类型
收费全文 | 3054篇 |
免费 | 152篇 |
国内免费 | 1篇 |
出版年
2024年 | 4篇 |
2023年 | 18篇 |
2022年 | 50篇 |
2021年 | 67篇 |
2020年 | 45篇 |
2019年 | 58篇 |
2018年 | 71篇 |
2017年 | 70篇 |
2016年 | 125篇 |
2015年 | 170篇 |
2014年 | 221篇 |
2013年 | 217篇 |
2012年 | 262篇 |
2011年 | 241篇 |
2010年 | 167篇 |
2009年 | 138篇 |
2008年 | 187篇 |
2007年 | 170篇 |
2006年 | 127篇 |
2005年 | 120篇 |
2004年 | 125篇 |
2003年 | 90篇 |
2002年 | 83篇 |
2001年 | 74篇 |
2000年 | 68篇 |
1999年 | 43篇 |
1998年 | 16篇 |
1997年 | 14篇 |
1996年 | 14篇 |
1995年 | 7篇 |
1994年 | 4篇 |
1993年 | 5篇 |
1992年 | 15篇 |
1991年 | 12篇 |
1990年 | 11篇 |
1989年 | 14篇 |
1988年 | 9篇 |
1987年 | 6篇 |
1986年 | 6篇 |
1985年 | 9篇 |
1984年 | 5篇 |
1983年 | 4篇 |
1982年 | 6篇 |
1979年 | 9篇 |
1978年 | 4篇 |
1975年 | 4篇 |
1974年 | 5篇 |
1973年 | 4篇 |
1972年 | 3篇 |
1968年 | 2篇 |
排序方式: 共有3207条查询结果,搜索用时 22 毫秒
61.
Background
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality in Vietnam and hypertension (HTN) is an important and prevalent risk factor for CVD in the adult Vietnamese population. Despite an increasing prevalence of HTN in this country, information about the awareness, treatment, and control of HTN is limited. The objectives of this study were to describe the prevalence, awareness, treatment, and control of HTN, and factors associated with these endpoints, in residents of a mountainous province in Vietnam.Methods
Data from 2,368 adults (age≥25 years) participating in a population-based survey conducted in 2011 in Thai Nguyen province were analyzed. All eligible participants completed a structured questionnaire and were examined by community health workers using a standardized protocol.Results
The overall prevalence of HTN in this population was 23%. Older age, male sex, and being overweight were associated with a higher odds of having HTN, while higher educational level was associated with a lower odds of having HTN. Among those with HTN, only 34% were aware of their condition, 43% of those who were aware they had HTN received treatment and, of these, 39% had their HTN controlled.Conclusions
Nearly one in four adults in Thai Nguyen is hypertensive, but far fewer are aware of this condition and even fewer have their blood pressure adequately controlled. Public health strategies increasing awareness of HTN in the community, as well as improvements in the treatment and control of HTN, remain needed to reduce the prevalence of HTN and related morbidity and mortality. 相似文献62.
63.
Migyeong Jo Sanghwan Ko Bora Hwang Sung-Won Min Ji Yeon Ha Ji Chul Lee Se-Eun Jang Sang Taek Jung 《Biotechnology and bioengineering》2020,117(8):i-i
The immunoglobulin G (IgG) molecule has a long circulating serum half-life (~3 weeks) through pH- dependent FcRn binding-mediated recycling. To hijack the intracellular trafficking and recycling mechanism of IgG as a way to extend serum persistence of non-antibody therapeutic proteins, we have evolved the ectodomain of a low-affinity human FcγRIIa for enhanced binding to the lower hinge and upper CH2 region of IgG, which is very far from the FcRn binding site (CH2–CH3 interface). High-throughput library screening enabled isolation of an FcγRIIa variant (2A45.1) with 32-fold increased binding affinity to human IgG1 Fc (equilibrium dissociation constant: 9.04 × 10−7 M for wild type FcγRIIa and 2.82 × 10−8 M for 2A45.1) and significantly improved affinity to mouse serum IgG compared to wild type human FcγRIIa. The in vivo pharmacokinetic profile of PD-L1 fused with engineered FcγRIIa (PD-L1–2A45.1) was compared with that of PD-L1 fused with wild type FcγRIIa (PD-L1–wild type FcγRIIa) and human PD-L1 in mice. PD-L1–2A45.1 showed 11.7- and 9.7-fold prolonged circulating half-life (t1/2) compared to PD-L1 when administered intravenously and intraperitoneally, respectively. In addition, the AUCinf of PD-L1–2A45.1 was two-fold higher compared to that of PD-L1–wild type FcγRIIa. These results demonstrate that engineered FcγRIIa fusion offers a novel and successful strategy for prolonging serum half-life of therapeutic proteins. 相似文献
64.
Background
Human serum albumin is the principal protein in human serum. It participates in regulation of plasma oncotic pressure and transports endogenous and exogenous ligands such as thyroxine, free fatty acids, bilirubin, and various drugs. Therefore, studying its ligand binding mechanism is important in understanding many functions of the protein.Scope of review
This review discusses the pleiotropic biochemical effects and their relevance to physiologic functions of albumin.Major conclusions
Although HSA is traditionally recognized for its ligand transport and oncotic effects in human circulation, our studies have revealed its participation in several other important physiological functions. In some instances, it may function as a catalyst. Pleiotropic properties of HSA have been exploited by development of recombinant HSA and its mutants, and the use of these recombinant proteins in studies with various biochemical and biophysical techniques. These studies allowed us to obtain new insights on the diverse roles of HSA in human physiology. The following aspects of HSA were discussed in this review: 1) HSA and its mutants' role in thyroxine transport, 2) structural details of the ligand binding functions of HSA to ligands such as warfarin, digoxin, halothane anesthetics, nitric oxide, bilirubin, free fatty acids, etc, and 3) the formation of modified albumin during myocardial ischemia, its diagnostic significance, and HSA's role in cardiovascular disease.General significance
The appreciation and understanding of structural details and new physiological roles has provided a renewed interest in HSA research. Specific structural information gained on various mechanisms of HSA–ligand interaction can be used to develop a model to better understand protein–drug interactions, aid in the development of new drugs with improved pharmacokinetic effects, and ultimately be used to improve the quality of healthcare. This article is part of a Special Issue entitled Serum Albumin. 相似文献65.
66.
Joon Ha Park Choong Hyun Lee In Hye Kim Ji Hyeon Ahn Jeong-Hwi Cho Bing Chun Yan Jae-Chul Lee Tae Hun Lee Jeong Yeol Seo Jun Hwi Cho Moo-Ho Won Il-Jun Kang 《Neurochemical research》2013,38(12):2640-2649
Glucose is a main energy source for normal brain functions. Glucokinase (GK) plays an important role in glucose metabolism as a glucose sensor, and GK activity is modulated by glucokinase regulatory protein (GKRP). In this study, we examined the changes of GK and GKRP immunoreactivities in the gerbil hippocampus after 5 min of transient global cerebral ischemia. In the sham-operated-group, GK and GKRP immunoreactivities were easily detected in the pyramidal neurons of the stratum pyramidale of the hippocampus. GK and GKRP immunoreactivities in the pyramidal neurons were distinctively decreased in the hippocampal CA1 region (CA), not CA2/3, 3 days after ischemia–reperfusion (I–R). Five days after I–R, GK and GKRP immunoreactivities were hardly detected in the CA1, not CA2/3, pyramidal neurons; however, at this point in time, GK and GKRP immunoreactivities were newly expressed in astrocytes, not microglia, in the ischemic CA1. In brief, GK and GKRP immunoreactivities are changed in pyramidal neurons and newly expressed in astrocytes in the ischemic CA1 after transient cerebral ischemia. These indicate that changes of GK and GKRP expression may be related to the ischemia-induced neuronal damage/death. 相似文献
67.
MicroRNAs (miRNAs) are small RNA molecules (~ 20–30 nucleotides) that generally act in gene silencing and translational repression through the RNA interference pathway. They generally originate from intergenic genomic regions, but some are found in genomic regions that have been characterized such as introns, exons, and transposable elements (TE). To identify the miRNAs that are derived from palindromic MERs, we analyzed MER paralogs in human genome. The structures of the palindromic MERs were similar to the hairpin structure of miRNA in humans. Three miRNAs derived from MER96 located on chromosome 3, and MER91C paralogs located on chromosome 8 and chromosome 17 were identified in HeLa, HCT116, and HEK293 cell lines. The interactions between these MER-derived miRNAs and AGO1, AGO2, and AGO3 proteins were validated by immunoprecipitation assays. The data suggest that miRNAs derived from transposable elements could widely affect various target genes in the human genome. 相似文献
68.
Keisuke Toyoda Kunihiko Tanaka Shinsuke Nakagawa Dinh Ha Duy Thuy Kenta Ujifuku Kensaku Kamada Kentaro Hayashi Takayuki Matsuo Izumi Nagata Masami Niwa 《Cellular and molecular neurobiology》2013,33(4):489-501
Glioblastoma multiforme (GBM) cells invade along the existing normal capillaries in brain. Normal capillary endothelial cells function as the blood–brain barrier (BBB) that limits permeability of chemicals into the brain. To investigate whether GBM cells modulate the BBB function of normal endothelial cells, we developed a new in vitro BBB model with primary cultures of rat brain endothelial cells (RBECs), pericytes, and astrocytes. Cells were plated on a membrane with 8 μm pores, either as a monolayer or as a BBB model with triple layer culture. The BBB model consisted of RBEC on the luminal side as a bottom, and pericytes and astrocytes on the abluminal side as a top of the chamber. Human GBM cell line, LN-18 cells, or lung cancer cell line, NCI-H1299 cells, placed on either the RBEC monolayer or the BBB model increased the transendothelial electrical resistance (TEER) values against the model, which peaked within 72 h after the tumor cell application. The TEER value gradually returned to baseline with LN-18 cells, whereas the value quickly dropped to the baseline in 24 h with NCI-H1299 cells. NCI-H1299 cells invaded into the RBEC layer through the membrane, but LN-18 cells did not. Fibroblast growth factor 2 (FGF-2) strengthens the endothelial cell BBB function by increased occludin and ZO-1 expression. In our model, LN-18 and NCI-H1299 cells secreted FGF-2, and a neutralization antibody to FGF-2 inhibited LN-18 cells enhanced BBB function. These results suggest that FGF-2 would be a novel therapeutic target for GBM in the perivascular invasive front. 相似文献
69.
Dae Hwan Lee Ji Hyeon Ahn Joon Ha Park Bing Chun Yan Jeong-Hwi Cho In Hye Kim Jae-Chul Lee Sang-Hun Jang Myoung Hyo Lee In Koo Hwang Seung Myung Moon Bonghee Lee Jun Hwi Cho Hyung-Cheul Shin Jin Sang Kim Moo-Ho Won 《Cellular and molecular neurobiology》2013,33(5):615-624
Aging is an inevitable process that occurs in the whole body system accompanying with many functional and morphological changes. Inflammation is known as one of age-related factors, and inflammatory changes could enhance mortality risk. In this study, we compared immunoreactivities of inflammatory cytokines, such as interleukin (IL)-2 (a pro-inflammatory cytokine), its receptor (IL-2R), IL-4 (an anti-inflammatory cytokine), and its receptor (IL-4R) in the cervical and lumbar spinal cord of young adult (2–3 years old) and aged (10–12 years old) beagle dogs using immunohistochemistry and western blotting. IL-2 and IL-2R-immunoreactive nerve cells were found throughout the gray matter of the cervical and lumbar spinal cord of young adult and aged dogs. In the spinal cord neurons of the aged dog, immunoreactivity and protein levels were apparently increased compared with those in the young adult dog. Change patterns of IL-4- and IL-4R-immunoreactive cells and their protein levels were also similar to those in IL-2 and IL-2R; however, IL-4 and IL-4R immunoreactivity in the periphery of the neuronal cytoplasm in the aged dog was much stronger than that in the young adult dog. These results indicate that the increase of inflammatory cytokines and their receptors in the aged spinal cord might be related to maintaining a balance of inflammatory reaction in the spinal cord during normal aging. 相似文献
70.
Nguyen Thi Dieu Thuy Nguyen Thi Thu Nguyen Giang Son Le Thi Thu Ha Vo Khanh Hung Nguyen Thao Nguyen Do Vo Anh Khoa 《Microbiology and immunology》2013,57(7):518-526
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important swine pathogens because it is highly infectious and causes economic losses due to decreased pig productivity. In this study, the 603 bp complete major envelope protein encoding gene (ORF5) of 32 field PRRSV isolates from Vietnam collected during 2008–2012 were sequenced and analyzed. Multiple nucleotide (nt) and deduced amino acid (aa) alignments of ORF5 were performed on the 32 isolates: the representative strains (European and North American genotypes), Chinese strains available in GenBank and vaccine strains licensed for use in Vietnam. The results showed 94.8–100.0% nt identity and 94.0–100% aa similarity among the 32 isolates. These isolates shared similarities with the prototype of the North American PRRSV strain (VR‐2332; nt 87.8–89.3%, aa 87.5–90.0%), and Lelystat virus, the prototype of the European PRRSV strain (LV; nt 61.1–61.9%, aa 55.1‐57.0%). There was greater similarity with QN07 (nt 96.5‐98.5%, aa 96.0‐99.0%) from the 2007 PRRS outbreak in QuangNam Province, CH‐1a (nt 93.2–95.1%, 91.5–93.5%) isolated in China in 1995 and JXA1 (nt 96.5–98.6%, aa 95.0–98.0%), the highly pathogenic strain from China isolated in 2006. The Vietnamese isolates were more similar to JXA1‐R (nt 96.5–98.6%, aa 95.0–98.0%), the strain used in Chinese vaccines, than to Ingelvac MLV/BSL‐PS (nt 87.2–89.0%, aa 86.0–89.0%). Phylogenetic analysis showed that the 32 isolates were of the North American genotype and classified into sub‐lineage 8.7. This sub‐lineage contains highly pathogenic Chinese PRRSV strains. This study documents genetic variation in circulating PRRSV strains and could assist more effective use of PRRS vaccines in Vietnam. 相似文献