全文获取类型
收费全文 | 11077篇 |
免费 | 864篇 |
国内免费 | 6篇 |
出版年
2023年 | 72篇 |
2022年 | 189篇 |
2021年 | 285篇 |
2020年 | 156篇 |
2019年 | 286篇 |
2018年 | 314篇 |
2017年 | 277篇 |
2016年 | 401篇 |
2015年 | 631篇 |
2014年 | 640篇 |
2013年 | 831篇 |
2012年 | 972篇 |
2011年 | 915篇 |
2010年 | 566篇 |
2009年 | 543篇 |
2008年 | 663篇 |
2007年 | 669篇 |
2006年 | 567篇 |
2005年 | 509篇 |
2004年 | 454篇 |
2003年 | 410篇 |
2002年 | 381篇 |
2001年 | 109篇 |
2000年 | 66篇 |
1999年 | 90篇 |
1998年 | 94篇 |
1997年 | 68篇 |
1996年 | 62篇 |
1995年 | 68篇 |
1994年 | 63篇 |
1993年 | 42篇 |
1992年 | 56篇 |
1991年 | 44篇 |
1990年 | 30篇 |
1989年 | 45篇 |
1988年 | 27篇 |
1987年 | 30篇 |
1986年 | 30篇 |
1985年 | 31篇 |
1984年 | 19篇 |
1983年 | 29篇 |
1982年 | 14篇 |
1981年 | 12篇 |
1980年 | 18篇 |
1979年 | 24篇 |
1978年 | 15篇 |
1977年 | 15篇 |
1974年 | 15篇 |
1972年 | 11篇 |
1968年 | 10篇 |
排序方式: 共有10000条查询结果,搜索用时 31 毫秒
11.
Niyati Jain Christopher E. Morgan Brittany D. Rife Marco Salemi Blanton S. Tolbert 《The Journal of biological chemistry》2016,291(5):2331-2344
Splicing patterns in human immunodeficiency virus type 1 (HIV-1) are maintained through cis regulatory elements that recruit antagonistic host RNA-binding proteins. The activity of the 3′ acceptor site A7 is tightly regulated through a complex network of an intronic splicing silencer (ISS), a bipartite exonic splicing silencer (ESS3a/b), and an exonic splicing enhancer (ESE3). Because HIV-1 splicing depends on protein-RNA interactions, it is important to know the tertiary structures surrounding the splice sites. Herein, we present the NMR solution structure of the phylogenetically conserved ISS stem loop. ISS adopts a stable structure consisting of conserved UG wobble pairs, a folded 2X2 (GU/UA) internal loop, a UU bulge, and a flexible AGUGA apical loop. Calorimetric and biochemical titrations indicate that the UP1 domain of heterogeneous nuclear ribonucleoprotein A1 binds the ISS apical loop site-specifically and with nanomolar affinity. Collectively, this work provides additional insights into how HIV-1 uses a conserved RNA structure to commandeer a host RNA-binding protein. 相似文献
12.
Giuseppe Corace Cristina Angeloni Marco Malaguti Silvana Hrelia Paul C. Stein Martin Brandl 《Journal of liposome research》2014,24(4):323-335
The purpose of this study was the development of multifunctional liposomes for nasal administration of tacrine hydrochloride. Liposomes were prepared using traditional excipients (cholesterol and phosphatidylcholine), partly enriched with α-tocopherol and/or Omega3 fatty acids. This approach was chosen in order to obtain at the same time two positive results: an enhanced drug permeation through nasal mucosa and a concomitant neuroprotective effect. Several liposome formulations were prepared using the Reverse Phase Evaporation technique followed by membrane filter extrusion. In particular, liposome capacity to enhance drug permeation was evaluated by means of membrane permeation and cellular uptake studies. Furthermore, liposome effect on neuronal viability and intracellular ROS production was evaluated as well as their cytoprotective effect against oxidative stress. All liposome formulations showed a mean diameter in the range of 175?nm to 219?nm with polydispersity index lower than 0.22, a lightly negative zeta potential and excellent encapsulation efficiency. Moreover, along with good mucoadhesive properties, multifunctional liposomes showed a markedly increase in tacrine permeability, which can be related to liposome fusion with cellular membrane, a hypothesis, which was also supported by cellular uptake studies. Finally, the addition of α-tocopherol without Omega3 fatty acids, was found to increase the neuroprotective activity and antioxidant properties of liposomes. 相似文献
13.
14.
Distinct effects of climate warming on populations of silver fir (Abies alba) across Europe
下载免费PDF全文
![点击此处可从《Journal of Biogeography》网站下载免费的PDF全文](/ch/ext_images/free.gif)
15.
Alberto Buson Alessandro Negro Luigi Grassato Massimo Tagliaro Marina Basaglia Claudio Grandi Angelo Fontana Marco P. Nuti 《FEMS microbiology letters》1996,145(1):55-62
Abstract A clone positive for d-carbamoylase activity (2.7 kb Hin dIII- Bam H1 DNA fragment) was obtained by screening a genomic library of Agrobacterium radiobacter in Escherichia coli . This DNA fragment contains an open reading frame of 912 bp which is predicted to encode a peptide of 304 amino acids with a calculated molecular mass of 34247 Da. The d-carbamoylase gene. named cauA , was placed under the control of T7 RNA-dependent promoter and expressed in E. coli BL21 (DE3). After induction with isopropyl-thio-β-d-galactopyranoside, the synthesis of d-carbamoylase in E. coli reached about 40% of the total protein. The expressed protein was shown to possess a molecular mass, on SDS-PAGE, of 36 kDa and showed an enhanced allowed us to establish that a Pro14 →Leu14 exchange leads to an inactive enzyme species, while a Cys279 →Ser279 exchange did not impair the functional properties of the enxyme. 相似文献
16.
Marina Burgos-Silva Patricia Semedo-Kuriki Cassiano Donizetti-Oliveira Priscilla Barbosa Costa Marco Antonio Cenedeze Meire Ioshie Hiyane Alvaro Pacheco-Silva Niels Olsen Saraiva Camara 《PloS one》2015,10(11)
Acute and chronic kidney injuries (AKI and CKI) constitute syndromes responsible for a large part of renal failures, and are today still associated with high mortality rates. Given the lack of more effective therapies, there has been intense focus on the use stem cells for organ protective and regenerative effects. Mesenchymal stem cells (MSCs) have shown great potential in the treatment of various diseases of immune character, although there is still debate on its mechanism of action. Thus, for a greater understanding of the role of MSCs, we evaluated the effect of adipose tissue-derived stem cells (AdSCs) in an experimental model of nephrotoxicity induced by folic acid (FA) in FVB mice. AdSC-treated animals displayed kidney functional improvement 24h after therapy, represented by reduced serum urea after FA. These data correlated with cell cycle regulation and immune response modulation via reduced chemokine expression and reduced neutrophil infiltrate. Long-term analyses, 4 weeks after FA, indicated that AdSC treatment reduced kidney fibrosis and chronic inflammation. These were demonstrated by reduced interstitial collagen deposition and tissue chemokine and cytokine expression. Thus, we concluded that AdSC treatment played a protective role in the framework of nephrotoxic injury via modulation of inflammation and cell cycle regulation, resulting in reduced kidney damage and functional improvement, inhibiting organ fibrosis and providing long-term immune regulation. 相似文献
17.
Sympathoadrenergic pathways are crucial to the communication between the nervous system and the immune system. The present review addresses emerging issues in the adrenergic modulation of immune cells, including: the specific pattern of adrenoceptor expression on immune cells and their role and changes upon cell differentiation and activation; the production and utilization of noradrenaline and adrenaline by immune cells themselves; the dysregulation of adrenergic immune mechanisms in disease and their potential as novel therapeutic targets. A wide array of sympathoadrenergic therapeutics is currently used for non-immune indications, and could represent an attractive source of non-conventional immunomodulating agents. 相似文献
18.
19.
Giorgio Trinchieri Marek Kubin Graziella Bellone Marco A. Cassatella 《Journal of cellular biochemistry》1993,53(4):301-308
Cytokines represent one of the most important elements in the communication among different cell types. They play an increasingly better understood role in the communication among hematopoietic cells and in particular in the reciprocal regulation of effector cell types of innate or natural resistance (phagocytic cells and Natural Killer (NK) cells) and those of adaptive immunity (T and B lymphocytes). Lymphocytes produce several cytokines with either stimulatory (e.g., colony stimulatory factor) or suppressive (e.g., tumor necrosis factors and interferons) effects on proliferation of early hematopoietic cells. Many of these cytokines, alone or acting in synergistic combinations, also have a differentiation-inducing ability on immature myeloid cells and act as powerful potentiators of the cellular functions of terminally differentiated phagocytic cells. The communication between lymphocytes and phagocytic cells is not unidirectional, as phagocytic cells produce factors that regulate lymphocyte activation. In addition to their role as antigen presenting cells expressing costimulatory accessory molecules and secreting cytokines (e.g., IL-1, IL-6, TNF), phagocytic cells have been recently shown to produce Natural Killer cell Stimulatory Factor (NKSF/IL-12). IL-12 is a heterodimeric cytokine with important modulatory functions on cytotoxicity of NK and T cells, lymphocyte proliferation, lymphokine production, and development of T helper cell subsets. These communications between phagocytic cells and lymphocytes are further regulated by negative and positive feedback mechanisms that contribute to maintain the homeostasis of the system in physiologic conditions and to govern the changes in this equilibrium needed for the response to infectious or other foreign agents. 相似文献
20.