全文获取类型
收费全文 | 1750篇 |
免费 | 199篇 |
专业分类
1949篇 |
出版年
2022年 | 20篇 |
2021年 | 31篇 |
2020年 | 16篇 |
2019年 | 26篇 |
2018年 | 33篇 |
2017年 | 23篇 |
2016年 | 34篇 |
2015年 | 61篇 |
2014年 | 63篇 |
2013年 | 82篇 |
2012年 | 79篇 |
2011年 | 100篇 |
2010年 | 59篇 |
2009年 | 48篇 |
2008年 | 73篇 |
2007年 | 83篇 |
2006年 | 57篇 |
2005年 | 60篇 |
2004年 | 63篇 |
2003年 | 64篇 |
2002年 | 69篇 |
2001年 | 48篇 |
2000年 | 50篇 |
1999年 | 53篇 |
1998年 | 20篇 |
1997年 | 19篇 |
1996年 | 19篇 |
1994年 | 13篇 |
1993年 | 15篇 |
1992年 | 31篇 |
1991年 | 25篇 |
1990年 | 30篇 |
1989年 | 39篇 |
1988年 | 30篇 |
1987年 | 23篇 |
1986年 | 21篇 |
1985年 | 19篇 |
1984年 | 20篇 |
1982年 | 19篇 |
1981年 | 25篇 |
1980年 | 14篇 |
1979年 | 16篇 |
1978年 | 12篇 |
1975年 | 14篇 |
1974年 | 17篇 |
1973年 | 21篇 |
1972年 | 15篇 |
1970年 | 14篇 |
1967年 | 16篇 |
1966年 | 16篇 |
排序方式: 共有1949条查询结果,搜索用时 15 毫秒
101.
Natasza M.R. Hain-Saunders Daniel R. Knight Mieghan Bruce Thomas V. Riley 《Environmental microbiology》2022,24(3):985-997
Clostridioides (Clostridium) difficile presents a significant health risk to humans and animals. The complexity of the bacterial–host interaction affecting pathogenesis and disease development creates an ongoing challenge for epidemiological studies, control strategies and prevention planning. The recent emergence of human disease caused by strains of C. difficile found in animals adds to mounting evidence that C. difficile infection (CDI) may be a zoonosis. In equine populations, C. difficile is a known cause of diarrhoea and gastrointestinal inflammation, with considerable mortality and morbidity. This has a significant impact on both the well-being of the animal and, in the case of performance and production animals, it may have an adverse economic impact on relevant industries. While C. difficile is regularly isolated from horses, many questions remain regarding the impact of asymptomatic carriage as well as optimization of diagnosis, testing and treatment. This review provides an overview of our understanding of equine CDI while also identifying knowledge gaps and the need for a holistic One Health approach to a complicated issue. 相似文献
102.
Amide hydrogen/deuterium exchange mass spectrometry (HDXMS) of proteins has become extremely popular for identifying ligand-binding sites, protein-protein interactions, intrinsic disorder, and allosteric changes upon protein modification. Such phenomena are revealed when amide exchange is measured in the fast limit, that is, within a few minutes of exchange in deuterated buffer. The HDXMS data have a resolution of the length of peptides and are difficult to interpret because many different phenomena lead to changes in hydrogen/deuterium exchange. We present a quantitative analysis of accelerated molecular dynamics simulations that provides impressive agreement with peptide-length HDXMS data. Comparative analysis of thrombin and a single-point mutant reveals that the simulation analysis can distinguish the subtle differences in exchange due to mutation. In addition, the results provide a deeper understanding of the underlying changes in dynamics revealed by the HDXMS that extend far from the site of mutation. 相似文献
103.
Agatha A. van der Klaauw Sophie Croizier Edson Mendes de Oliveira Lukas K.J. Stadler Soyoung Park Youxin Kong Matthew C. Banton Panna Tandon Audrey E. Hendricks Julia M. Keogh Susanna E. Riley Sofia Papadia Elana Henning Rebecca Bounds Elena G. Bochukova Vanisha Mistry Stephen O’Rahilly Richard B. Simerly I. Sadaf Farooqi 《Cell》2019,176(4):729-742.e18
104.
Leigh‐Ann Woolley Hayley M. Geyle Brett P. Murphy Sarah M. Legge Russell Palmer Christopher R. Dickman John Augusteyn Sarah Comer Tim S. Doherty Charlie Eager Glenn Edwards Dan K.P. Harley Ian Leiper Peter J. McDonald Hugh W. McGregor Katherine E. Moseby Cecilia Myers John L. Read Joanna Riley Danielle Stokeld Jeff M. Turpin John C.Z. Woinarski 《Mammal Review》2019,49(4):354-368
- 相似文献
105.
Nicole R. Foster Korjent van Dijk Ed Biffin Jennifer M. Young Vicki A. Thomson Bronwyn M. Gillanders Alice R. Jones Michelle Waycott 《Ecology and evolution》2022,12(4)
Metabarcoding has improved the way we understand plants within our environment, from their ecology and conservation to invasive species management. The notion of identifying plant taxa within environmental samples relies on the ability to match unknown sequences to known reference libraries. Without comprehensive reference databases, species can go undetected or be incorrectly assigned, leading to false‐positive and false‐negative detections. To improve our ability to generate reference sequence databases, we developed a targeted capture approach using the OZBaits_CP V1.0 set, designed to capture chloroplast gene regions across the entirety of flowering plant diversity. We focused on generating a reference database for coastal temperate plant species given the lack of reference sequences for these taxa. Our approach was successful across all specimens with a target gene recovery rate of 92%, which was achieved in a single assay (i.e., samples were pooled), thus making this approach much faster and more efficient than standard barcoding. Further testing of this database highlighted 80% of all samples could be discriminated to family level across all gene regions with some genes achieving greater resolution than others—which was also dependent on the taxon of interest. Thus, we demonstrate the importance of generating reference sequences across multiple chloroplast gene regions as no single loci are sufficient to discriminate across all plant groups. The targeted capture approach outlined in this study provides a way forward to achieve this. 相似文献
106.
Understanding propulsion and adaptation to speed requirements is important in determining appropriate therapies for gait disorders. We hypothesize that adaptations for changing speed requirements occur primarily at the hip. The slow, normal and fast gait of 24 healthy young subjects was analyzed. The linear power was analyzed at the hip joint. The anterior-posterior and vertical induced accelerations of the hip were also determined. Linear power and anterior-posterior-induced acceleration (IA) analyses of the hip reveal that the lower limb joint's moments contribute to body forward propulsion primarily during late swing and early stance. Propulsive adaptations to speed changes occur primarily at the hip and secondarily at the ankle. These analyses show that hip muscles, particularly the hip extensors, are critical to propulsion. They also show that ankle function is primarily for support, but is important to propulsion, especially at slow speeds. 相似文献
107.
BACKGROUND: Fate mapping studies have shown that progenitor cells of three vertebrate embryonic midline structures - the floorplate in the ventral neural tube, the notochord and the dorsal endoderm - occupy a common region prior to gastrulation. This common region of origin raises the possibility that interactions between midline progenitor cells are important for their specification prior to germ layer formation. RESULTS: One of four known zebrafish homologues of the Drosophila melanogaster cell-cell signaling gene Delta, deltaA (dlA), is expressed in the developing midline, where progenitor cells of the ectodermal floorplate, mesodermal notochord and dorsal endoderm lie close together before they occupy different germ layers. We used a reverse genetic strategy to isolate a missense mutation of dlA, dlAdx2, which coordinately disrupts the development of floorplate, notochord and dorsal endoderm. The dlAdx2 mutant embryos had reduced numbers of floorplate and hypochord cells; these cells lie above and beneath the notochord, respectively. In addition, mutant embryos had excess notochord cells. Expression of a dominant-negative form of Delta protein driven by mRNA microinjection produced a similar effect. In contrast, overexpression of dlA had the opposite effect: fewer trunk notochord cells and excess floorplate and hypochord cells. CONCLUSION: Our results indicate that Delta signaling is important for the specification of midline cells. The results are most consistent with the hypothesis that developmentally equivalent midline progenitor cells require Delta-mediated signaling prior to germ layer formation in order to be specified as floorplate, notochord or hypochord. 相似文献
108.
The first discovered naturally occurring inhibitor of de novo sphingolipid biosynthesis was fumonisin B1. There are now 11 identified fungal inhibitors of ceramide synthase or 'fumonisin B1-like' compounds. With the exception of the australifungins, all other fungal ceramide synthase inhibitors are structurally sphingoid-like. There are several recently discovered fungal inhibitors of another enzyme in the de novo sphingolipid biosynthesis pathway: serine palmitoyltransferase (SPT). One of the SPT inhibitors is named ISP-I. While ceramide synthase inhibitors are toxic to animals, plants and fungi, the SPT inhibitors are not known to cause animal or plant disease, but are potent inhibitors of fungal growth. Very little is known about their toxicity in animals. There are at least 24 fungal SPT inhibitors produced by a variety of fungi. Given that the fungal inhibitors of sphingolipid biosynthesis are chemically and biologically diverse, two bioassays have been developed to screen for fumonisin-like or ISP-I-like activity in naturally contaminated products or fungal culture materials. These bioassays are based on the changes in free sphingoid base concentration that occur when the ceramide synthase or SPT are inhibited. The bioassays have the advantage that they are functionally rather than chemically specific and thus will detect ceramide synthase and SPT inhibitors regardless of their chemical structure. 相似文献
109.
The residues between the two transformation effector sites of Epstein-Barr virus latent membrane protein 1 are not critical for B-lymphocyte growth transformation
下载免费PDF全文
![点击此处可从《Journal of virology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Izumi KM Cahir McFarland ED Riley EA Rizzo D Chen Y Kieff E 《Journal of virology》1999,73(12):9908-9916
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is essential for EBV-mediated transformation of primary B lymphocytes. LMP1 spontaneously aggregates in the plasma membrane and enables two transformation effector sites (TES1 and TES2) within the 200-amino-acid cytoplasmic carboxyl terminus to constitutively engage the tumor necrosis factor receptor (TNFR)-associated factors TRAF1, TRAF2, TRAF3, and TRAF5 and the TNFR-associated death domain proteins TRADD and RIP, thereby activating NF-kappaB and c-Jun N-terminal kinase (JNK). To investigate the importance of the 60% of the LMP1 carboxyl terminus that lies between the TES1-TRAF and TES2-TRADD and -RIP binding sites, an EBV recombinant was made that contains a specific deletion of LMP1 codons 232 to 351. Surprisingly, the deletion mutant was similar to wild-type (wt) LMP1 EBV recombinants in its efficiency in transforming primary B lymphocytes into lymphoblastoid cell lines (LCLs). Mutant and wt EBV-transformed LCLs were similarly efficient in long-term outgrowth and in regrowth after endpoint dilution. Mutant and wt LMP1 proteins were also similar in their constitutive association with TRAF1, TRAF2, TRAF3, TRADD, and RIP. Mutant and wt EBV-transformed LCLs were similar in steady-state levels of Bcl2, JNK, and activated JNK proteins. The wt phenotype of recombinants with LMP1 codons 232 to 351 deleted further demarcates TES1 and TES2, underscores their central importance in B-lymphocyte growth transformation, and provides a new perspective on LMP1 sequence variation between TES1 and TES2. 相似文献
110.
Riley DE Krieger JN 《BioEssays : news and reviews in molecular, cellular and developmental biology》2004,26(4):434-444
Within the genomes of multicellular organisms, short tandem repeating sequences (STRs) are ubiquitous, yet usage patterns remain obscure. The repeats (AC)n and (GU)n appear frequently in the untranslated regions (UTRs) of messenger RNAs (mRNAs). To investigate STR usage patterns, we used three approaches: (1) comparisons of individual mRNA database sequences including annotations and linked references, (2) statistical analysis of complete, UTR databases and (3) study of a large gene family, the aquaporins. Among 500 (AC)n- or (GU)n-containing mRNAs, 58 (12%) had known functions. Of these, 50 (86%) encoded proteins whose activities involved membranes or lipids, including integral membrane proteins, peripheral membrane proteins, ion channels, lipid enzymes, receptors and secreted proteins. A control sequence (AU)n also occurred in mRNAs, but only 5% encoded membrane-related functions. Investigation of all reported 3' UTR sequences, demonstrated that the STR (AC)n was 9 times more common in mRNAs encoding membrane functions than in the total UTR database (P < 0.001). Similarly, (GU)n was 8 times more common in membrane-function mRNAs than in the total database (P < 0.001). These observations suggest that (AC)n and (GU)n may be UTR signals for some mRNAs encoding membrane-targeted proteins. 相似文献