全文获取类型
收费全文 | 901篇 |
免费 | 88篇 |
专业分类
989篇 |
出版年
2022年 | 10篇 |
2021年 | 15篇 |
2019年 | 11篇 |
2018年 | 13篇 |
2017年 | 7篇 |
2016年 | 19篇 |
2015年 | 31篇 |
2014年 | 40篇 |
2013年 | 40篇 |
2012年 | 39篇 |
2011年 | 41篇 |
2010年 | 25篇 |
2009年 | 39篇 |
2008年 | 46篇 |
2007年 | 41篇 |
2006年 | 27篇 |
2005年 | 43篇 |
2004年 | 47篇 |
2003年 | 39篇 |
2002年 | 29篇 |
2001年 | 16篇 |
2000年 | 25篇 |
1999年 | 28篇 |
1998年 | 10篇 |
1997年 | 9篇 |
1996年 | 8篇 |
1995年 | 11篇 |
1994年 | 8篇 |
1992年 | 25篇 |
1991年 | 23篇 |
1990年 | 7篇 |
1989年 | 14篇 |
1988年 | 16篇 |
1987年 | 7篇 |
1986年 | 15篇 |
1985年 | 11篇 |
1984年 | 9篇 |
1983年 | 9篇 |
1982年 | 6篇 |
1981年 | 6篇 |
1980年 | 7篇 |
1979年 | 15篇 |
1978年 | 10篇 |
1977年 | 9篇 |
1976年 | 7篇 |
1975年 | 9篇 |
1974年 | 9篇 |
1973年 | 7篇 |
1964年 | 5篇 |
1937年 | 4篇 |
排序方式: 共有989条查询结果,搜索用时 0 毫秒
81.
Nicholas J. Gotelli Faye Moyes Laura H. Anto Shane A. Blowes Maria Dornelas Brian J. McGill Amelia Penny Aafke M. Schipper Hideyasu Shimadzu Sarah R. Supp Conor A. Waldock Anne E. Magurran 《Global Change Biology》2022,28(1):46-53
The species composition of plant and animal assemblages across the globe has changed substantially over the past century. How do the dynamics of individual species cause this change? We classified species into seven unique categories of temporal dynamics based on the ordered sequence of presences and absences that each species contributes to an assemblage time series. We applied this framework to 14,434 species trajectories comprising 280 assemblages of temperate marine fishes surveyed annually for 20 or more years. Although 90% of the assemblages diverged in species composition from the baseline year, this compositional change was largely driven by only 8% of the species' trajectories. Quantifying the reorganization of assemblages based on species shared temporal dynamics should facilitate the task of monitoring and restoring biodiversity. We suggest ways in which our framework could provide informative measures of compositional change, as well as leverage future research on pattern and process in ecological systems. 相似文献
82.
Brigl M van den Elzen P Chen X Meyers JH Wu D Wong CH Reddington F Illarianov PA Besra GS Brenner MB Gumperz JE 《Journal of immunology (Baltimore, Md. : 1950)》2006,176(6):3625-3634
CD1d-restricted NKT cells use structurally conserved TCRs and recognize both self and foreign glycolipids, but the TCR features that determine these Ag specificities remain unclear. We investigated the TCR structures and lipid Ag recognition properties of five novel Valpha24-negative and 13 canonical Valpha24-positive/Vbeta11-positive human NKT cell clones generated using alpha-galactosylceramide (alpha-GalCer)-loaded CD1d tetramers. The Valpha24-negative clones expressed Vbeta11 paired with Valpha10, Valpha2, or Valpha3. Strikingly, their Valpha-chains had highly conserved rearrangements to Jalpha18, resulting in CDR3alpha loop sequences that are nearly identical to those of canonical TCRs. Valpha24-positive and Valpha24-negative clones responded similarly to alpha-GalCer and a closely related bacterial analog, suggesting that conservation of the CDR3alpha loop is sufficient for recognition of alpha-GalCer despite CDR1alpha and CDR2alpha sequence variation. Unlike Valpha24-positive clones, the Valpha24-negative clones responded poorly to a glucose-linked glycolipid (alpha-glucosylceramide), which correlated with their lack of a conserved CDR1alpha amino acid motif, suggesting that fine specificity for alpha-linked glycosphingolipids is influenced by Valpha-encoded TCR regions. Valpha24-negative clones showed no response to isoglobotrihexosylceramide, indicating that recognition of this mammalian lipid is not required for selection of Jalpha18-positive TCRs that can recognize alpha-GalCer. One alpha-GalCer-reactive, Valpha24-positive clone differed from the others in responding specifically to mammalian phospholipids, demonstrating that semi-invariant NKT TCRs have a capacity for private Ag specificities that are likely conferred by individual TCR beta-chain rearrangements. These results highlight the variation in Ag recognition among CD1d-restricted TCRs and suggest that TCR alpha-chain elements contribute to alpha-linked glycosphingolipid specificity, whereas TCR beta-chains can confer heterogeneous additional reactivities. 相似文献
83.
The DNA translocase RAD5A acts independently of the other main DNA repair pathways,and requires both its ATPase and RING domain for activity in Arabidopsis thaliana 下载免费PDF全文
Tobias Klemm Anja Mannuß Daniela Kobbe Alexander Knoll Oliver Trapp Annika Dorn Holger Puchta 《The Plant journal : for cell and molecular biology》2017,91(4):725-740
Multiple pathways exist to repair DNA damage induced by methylating and crosslinking agents in Arabidopsis thaliana. The SWI2/SNF2 translocase RAD5A, the functional homolog of budding yeast Rad5 that is required for the error‐free branch of post‐replicative repair, plays a surprisingly prominent role in the repair of both kinds of lesions in Arabidopsis. Here we show that both the ATPase domain and the ubiquitination function of the RING domain of the Arabidopsis protein are essential for the cellular response to different forms of DNA damage. To define the exact role of RAD5A within the complex network of DNA repair pathways, we crossed the rad5a mutant line with mutants of different known repair factors of Arabidopsis. We had previously shown that RAD5A acts independently of two main pathways of replication‐associated DNA repair defined by the helicase RECQ4A and the endonuclease MUS81. The enhanced sensitivity of all double mutants tested in this study indicates that the repair of damaged DNA by RAD5A also occurs independently of nucleotide excision repair (AtRAD1), single‐strand break repair (AtPARP1), as well as microhomology‐mediated double‐strand break repair (AtTEB). Moreover, RAD5A can partially complement for a deficient AtATM‐mediated DNA damage response in plants, as the double mutant shows phenotypic growth defects. 相似文献
84.
Malaria is one of the most prevalent infectious diseases worldwide with more than 250 million cases and one million deaths each year. One of the well-characterized malarial-related molecules is hemozoin (HZ), which is a dark-brown crystal formed by the parasite and released into the host during the burst of infected red blood cells. HZ has a stimulatory effect on the host immune system such as its ability to induce pro-inflammatory mediators responsible for some of the malaria related clinical symptoms such as fever. However, the host serum proteins interacting with malarial HZ as well as how this interaction modifies its recognition by phagocytes remained elusive. In the actual study, using proteomic liquid chromatographic mass spectrometry (LC-MS/MS) and immunochemical approaches, we compared the serum protein profiles of malaria patients and healthy individuals. Particularly, we utilized the malarial HZ itself to capture serum proteins capable to bind to HZ, enabling us to identify several proteins such as apolipoprotein E (ApoE), serum amyloid A (SAA), gelsolin, complement factor H and fibrinogen that were found to differ among healthy and malaria individual. Of particular interest is LPS binding protein (LBP), which is reported herein for the first time in the context of malaria. LBP is usually produced during innate inflammatory response to gram-negative bacterial infections. The exact role of these biomarkers and acute phase responses in malaria in general and HZ in particular remains to be investigated. The identification of these inflammation-related biomarkers in malaria paves the way to potentially utilize them as diagnostic and therapeutic targets. 相似文献
85.
Gagliardo B Faye A Jaouen M Deschemin JC Canonne-Hergaux F Vaulont S Sari MA 《The FEBS journal》2008,275(15):3793-3803
Hepcidin is a liver produced cysteine-rich peptide hormone that acts as the central regulator of body iron metabolism. Hepcidin is synthesized under the form of a precursor, prohepcidin, which is processed to produce the biologically active mature 25 amino acid peptide. This peptide is secreted and acts by controlling the concentration of the membrane iron exporter ferroportin on intestinal enterocytes and macrophages. Hepcidin binds to ferroportin, inducing its internalization and degradation, thus regulating the export of iron from cells to plasma. The aim of the present study was to develop a novel method to produce human and mouse recombinant hepcidins, and to compare their biological activity towards their natural receptor ferroportin. Hepcidins were expressed in Escherichia coli as thioredoxin fusion proteins. The corresponding peptides, purified after cleavage from thioredoxin, were properly folded and contained the expected four-disulfide bridges without the need of any renaturation or oxidation steps. Human and mouse hepcidins were found to be biologically active, promoting ferroportin degradation in macrophages. Importantly, biologically inactive aggregated forms of hepcidin were observed depending on purification and storage conditions, but such forms were unrelated to disulfide bridge formation. 相似文献
86.
Molecular and Genetic Characterization of Propionicin F, a Bacteriocin from Propionibacterium freudenreichii 下载免费PDF全文
Dag Anders Brede Therese Faye Ola Johnsborg Inger
degrd Ingolf F. Nes Helge Holo 《Applied microbiology》2004,70(12):7303-7310
This work describes the purification and characterization of propionicin F, the first bacteriocin isolated from Propionibacterium freudenreichii. The bacteriocin has a bactericidal activity and is only active against strains of P. freudenreichii. Propionicin F appears to be formed through a processing pathway new to bacteriocins. The mass of the purified bacteriocin was determined by mass spectrometry, and the N-terminal amino acid sequence was determined by Edman degradation. Sequencing of pcfA, the bacteriocin structural gene, revealed that propionicin F corresponds to a 43-amino-acid peptide in the central part of a 255-amino-acid open reading frame, suggesting that mature propionicin F is excised from the probacteriocin by N- and C-terminal proteolytic modifications. DNA sequencing and Northern blot hybridizations revealed that pcfA is cotranscribed with genes encoding a putative proline peptidase and a protein from the radical S-adenosylmethionine family. A gene encoding an ABC transporter was also identified in close proximity to the bacteriocin structural gene. The potential role of these genes in propionicin F maturation and secretion is discussed. 相似文献
87.
Prior to the completion of the Human Genome Project, bioethicists and other academics debated the impact of this new genetic information on medicine, health care, group identification, and peoples’ lives. A major issue is the potential for unintended and intended adverse consequences to groups and individuals. When conducting research in, for instance, American Indian and Alaskan native (AI/AN) populations, political, cultural, religious and historical issues must be considered. Among African Americans, the Tuskegee Syphilis Experiment is a reminder of racism and discrimination in this country. The goal of the current study is to understand reasons for participating, or not, in genetic research such as the HapMap project and other genetic/medical research from the perspective of the Indian American community in Houston, Texas. In this article, we report on a topic central to this discussion among Indian Americans: karma and reincarnation. Both concepts are important beliefs when considering the body and what should happen to it. Karma and reincarnation are also important considerations in participation in medical and genetic research because, according to karma, what is done to the body can affect future existences and the health of future descendants. Such views of genetic and medical research are culturally mediated. Spiritual beliefs about the body, tissue, and fluids and what happens to them when separated from the body can influence ideas about the utility and acceptability of genetic research and thereby affect the recruitment process. Within this community it is understood that genetic and environmental factors contribute to complex diseases such as diabetes, hypertension, and cancer; and acknowledgment of the significance of environmental stressors in the production of disease. A commitment to service, i.e. “betterment of humanity,” karmic beliefs, and targeting environmental stressors could be prominent avenues for public health campaigns in this population. This study suggests that minority status does not automatically indicate unwillingness to participate in genetic or medical research. Indian Americans were not skeptical about the potential benefits of biomedical research in comparison to other ethnic minority communities in the United States. 相似文献
88.
Fabien Knoll 《Geobios》2008,41(6):779
A review of the historical background of the material housed in the Staatliches Museum für Naturkunde (Stuttgart) and ascribed to Procompsognathus triassicus (Upper Triassic, Germany) is provided. The systematic position of the postcranial remains is discussed. The combined results of cladistic analyses suggest that the type material, an incomplete postcranial skeleton in two pieces (SMNS 12591), is from a theropod close to Segisaurus and Coelophysis. An isolated manus (SMNS 12352a) is definitely not theropodan, but could be from any small basal archosaur. The remarkable diversity of the carnivorous guild that dwelled in southern Germany before the end-Triassic events is underlined. 相似文献
89.
Meriem Benchabane Claude Saint‐Jore‐Dupas Muriel Bardor Loïc Faye Dominique Michaud Véronique Gomord 《Plant biotechnology journal》2009,7(2):146-160
The post‐translational processing of human α1‐antichymotrypsin (AACT) in Bright Yellow‐2 (BY‐2) tobacco cells was assessed in relation to the cellular compartment targeted for accumulation. As determined by pulse‐chase labelling experiments and immunofluorescence microscopy, AACT sent to the vacuole or the endoplasmic reticulum (ER) was found mainly in the culture medium, similar to a secreted form targeted to the apoplast. Unexpectedly, AACT expressed in the cytosol was found in the nucleus under a stable, non‐glycosylated form, in contrast with secreted variants undergoing multiple post‐translational modifications during their transit through the secretory pathway. All secreted forms of AACT were N‐glycosylated, with the presence of complex glycans as observed naturally on human AACT. Proteolytic trimming was also observed for all secreted variants, both during their intracellular transit and after their secretion in the culture medium. Overall, the targeting of human AACT to different compartments of BY‐2 tobacco cells led to the production of two protein products: (i) a stable, non‐glycosylated protein accumulated in the nucleus; and (ii) a heterogeneous mixture of secreted variants resulting from post‐translational N‐glycosylation and proteolytic processing. Overall, these data suggest that AACT is sensitive to resident proteases in the ER, the Golgi and/or the apoplast, and that the production of intact AACT in the plant secretory pathway will require innovative approaches to protect its structural integrity in vivo. Studies are now needed to assess the activity of the different AACT variants, and to identify the molecular determinants for the nuclear localization of AACT expressed in the cytosol. 相似文献
90.