全文获取类型
收费全文 | 904篇 |
免费 | 109篇 |
出版年
2023年 | 2篇 |
2022年 | 15篇 |
2021年 | 22篇 |
2020年 | 6篇 |
2019年 | 22篇 |
2018年 | 21篇 |
2017年 | 10篇 |
2016年 | 33篇 |
2015年 | 43篇 |
2014年 | 47篇 |
2013年 | 52篇 |
2012年 | 84篇 |
2011年 | 61篇 |
2010年 | 51篇 |
2009年 | 43篇 |
2008年 | 56篇 |
2007年 | 55篇 |
2006年 | 50篇 |
2005年 | 40篇 |
2004年 | 44篇 |
2003年 | 37篇 |
2002年 | 36篇 |
2001年 | 18篇 |
2000年 | 9篇 |
1999年 | 15篇 |
1998年 | 22篇 |
1997年 | 9篇 |
1996年 | 7篇 |
1995年 | 9篇 |
1994年 | 5篇 |
1993年 | 4篇 |
1992年 | 13篇 |
1991年 | 6篇 |
1990年 | 4篇 |
1989年 | 8篇 |
1988年 | 2篇 |
1987年 | 4篇 |
1986年 | 5篇 |
1985年 | 4篇 |
1982年 | 6篇 |
1981年 | 4篇 |
1980年 | 3篇 |
1978年 | 2篇 |
1977年 | 2篇 |
1975年 | 2篇 |
1974年 | 3篇 |
1973年 | 3篇 |
1970年 | 3篇 |
1966年 | 2篇 |
1958年 | 1篇 |
排序方式: 共有1013条查询结果,搜索用时 15 毫秒
81.
A computational proposal for designing structured RNA pools for in vitro selection of RNAs 总被引:3,自引:0,他引:3
Although in vitro selection technology is a versatile experimental tool for discovering novel synthetic RNA molecules, finding complex RNA molecules is difficult because most RNAs identified from random sequence pools are simple motifs, consistent with recent computational analysis of such sequence pools. Thus, enriching in vitro selection pools with complex structures could increase the probability of discovering novel RNAs. Here we develop an approach for engineering sequence pools that links RNA sequence space regions with corresponding structural distributions via a "mixing matrix" approach combined with a graph theory analysis. We define five classes of mixing matrices motivated by covariance mutations in RNA; these constructs define nucleotide transition rates and are applied to chosen starting sequences to yield specific nonrandom pools. We examine the coverage of sequence space as a function of the mixing matrix and starting sequence via clustering analysis. We show that, in contrast to random sequences, which are associated only with a local region of sequence space, our designed pools, including a structured pool for GTP aptamers, can target specific motifs. It follows that experimental synthesis of designed pools can benefit from using optimized starting sequences, mixing matrices, and pool fractions associated with each of our constructed pools as a guide. Automation of our approach could provide practical tools for pool design applications for in vitro selection of RNAs and related problems. 相似文献
82.
SUMMARY: Our RNA-As-Graph-Pools (RagPools) web server offers a theoretical companion tool for RNA in vitro selection and related problems. Specifically, it suggests how to construct RNA sequence/structure pools with user-specified properties and assists in analyzing resulting distributions. This utility follows our recently developed approach for engineering sequence pools that links RNA sequence space regions with corresponding structural distributions via a 'mixing matrix' approach combined with a graph theory analysis of RNA secondary-structure space; the mixing matrix specifies nucleotide transition rates, and graph theory links sequences to simple graphical objects representing RNA motifs. The companion RagPools web server ('Designer' component) provides optimized starting sequences, mixing matrices and associated weights in response to a user-specified target pool structure distribution. In addition, RagPools ('Analyzer' component) analyzes the motif distribution of pools generated from user-specified starting sequences and mixing matrices. Thus, RagPools serves as a guide to researchers who aim to synthesize RNA pools with desired properties and/or experiment in silico with various designs by our approach. AVAILABILITY: The web server is accessible on the web at http://rubin2.biomath.nyu.edu 相似文献
83.
84.
Examples of animals that switch activity times between nocturnality and diurnality in nature are relatively infrequent. Furthermore, the mechanism for switching activity time is not clear: does a complete inversion of the circadian system occur in conjunction with activity pattern? Are there switching centers downstream from the internal clock that interpret the clock differently? Or does the switch reflect a masking effect? Answering these key questions may shed light on the mechanisms regulating activity patterns and their evolution. The golden spiny mouse (Acomys russatus) can switch between nocturnal and diurnal activity. This study investigated the relationship between its internal circadian clock and its diurnal activity pattern observed in the field. The goal is to understand the mechanisms underlying species rhythm shifts in order to gain insight into the evolution of activity patterns. All golden spiny mice had opposite activity patterns in the field than those under controlled continuous dark conditions in the laboratory. Activity and body temperature patterns in the field were diurnal, while in the laboratory all individuals immediately showed a free-running rhythm starting with a nocturnal pattern. No phase transients were found toward the preferred nocturnal activity pattern, as would be expected in the case of true entrainment. Moreover, the fact that the free-running activity patterns began from the individuals' subjective night suggests that golden spiny mice are nocturnal and that their diurnality in their natural habitat in the field results from a change that is downstream to the internal clock or reflects a masking effect. 相似文献
85.
Analysis of the three-dimensional structures of three closely related mesophilic, thermophilic, and hyperthermophilic alcohol dehydrogenases (ADHs) from the respective microorganisms Clostridium beijerinckii (CbADH), Entamoeba histolytica (EhADH1), and Thermoanaerobacter brockii (TbADH) suggested that a unique, strategically located proline residue (Pro100) might be crucial for maintaining the thermal stability of EhADH1. To determine whether proline substitution at this position in TbADH and CbADH would affect thermal stability, we used site-directed mutagenesis to replace the complementary residues in both enzymes with proline. The results showed that replacing Gln100 with proline significantly enhanced the thermal stability of the mesophilic ADH: DeltaT(1/2) (60 min) = + 8 degrees C (temperature of 50% inactivation after incubation for 60 min), DeltaT(1/2) (CD) = +11.5 degrees C (temperature at which 50% of the original CD signal at 218 nm is lost upon heating between 30 degrees and 98 degrees C). A His100 --> Pro substitution in the thermophilic TbADH had no effect on its thermostability. An analysis of the three-dimensional structure of the crystallized thermostable mutant Q100P-CbADH suggested that the proline residue at position 100 stabilized the enzyme by reinforcing hydrophobic interactions and by reducing the flexibility of a loop at this strategic region. 相似文献
86.
Synchronization of cell death in a dinoflagellate population is mediated by an excreted thiol protease 总被引:3,自引:0,他引:3
Vardi A Eisenstadt D Murik O Berman-Frank I Zohary T Levine A Kaplan A 《Environmental microbiology》2007,9(2):360-369
Regulated programmed cell death (PCD) processes have been documented in several phytoplankton species and are hypothesized to play a role in population dynamics. However, the mechanisms leading to the coordinated collapse of phytoplankton blooms are poorly understood. We showed that the collapse of the annual bloom of Peridinium gatunense, an abundant dinoflagellate in Lake Kinneret, Israel, is initiated by CO2 limitation followed by oxidative stress that triggers a PCD-like cascade. We provide evidences that a protease excreted by senescing P. gatunense cells sensitizes younger cells to oxidative stress and may consequently trigger synchronized cell death of the population. Ageing of the P. gatunense cultures was characterized by a remarkable rise in DNA fragmentation and enhanced sensitivity to H2O2. Exposure of logarithmic phase (young) cultures to conditioning media from stationary phase (old) cells sensitized them to H2O2 and led to premature massive cell death. We detected the induction of specific extracellular protease activity, leupeptin-sensitive, in ageing cultures and in lake waters during the succession of the P. gatunense bloom. Partial purification of the conditioned media revealed that this protease activity is responsible for the higher susceptibility of young cells to oxidative stress. Inhibition of the protease activity lowered the sensitivity to oxidative stress, whereas application of papain to logarithmic phase P. gatunense cultures mimicked the effect of the spent media and enhanced cell death. We propose a novel mechanistic framework by which a population of unicellular phytoplankton orchestrates a coordinated response to stress, thereby determine the fate of its individuals. 相似文献
87.
Non-indigenous species cause great damage worldwide. Non-indigenous insects are known as harmful in many regions, but few
comprehensive works have investigated non-indigenous insects as a group. We compiled a comprehensive database of established
non-indigenous (ENI) insects in Israel and adjacent regions to investigate how they arrived, their biological characteristics,
and the attributes of areas they invade. Of 218 species of ENI insects in this region, 124 are widespread. Most species came
as stowaways, but 38 were brought intentionally for biological control. Most ENI insects in this region are in the Coleoptera,
Diptera, Hymenoptera, Lepidoptera, and Homoptera. Species from various orders differ in their tendency to be localized or
widespread, and in biogeographic origins. The distribution of species among orders differs between native and ENI insects.
The Coastal Plain houses the most ENI insect species and the Negev and Judean deserts the fewest. Most ENI insects spread
from the Coastal Plain to other regions. Absence of roads, settlements and presence of nature reserves are negatively correlated
with occurrence of ENI species. Seventy-nine species are categorized as pests that damage produce, merchandise, forestry,
etc. Despite a general dearth of knowledge on impacts of ENI insects on natural systems, 42 species are known to feed on native
plants, some of conservation concern. Biological control agents are usually more limited in their distribution than other
ENI insects. Further research, legislation, and enforcement are required to minimize effects of these species on agriculture
and natural habitats. 相似文献
88.
Follicular dendritic cell sarcomas (FDCS) are rare tumours of lymph nodes and extranodal tissues which are grouped with the histiocytic and dendritic cell neoplasms. The diagnosis is usually made after thorough clinical and pathological examination with immunohistochemical analysis. Difficulties persist in diagnosing FDCS on cytological preparations. We report herein a case of a 57-year-old female who presented with a right neck mass of 5 months duration. Computed Tomography (CT) imaging of the neck reported a necrotic right level IIb lymph node and asymmetric fullness of the right palatine tonsil. Fine needle aspiration (FNA) biopsy revealed numerous spindle, oval and stellate neoplastic cells, arranged singly and in syncytia with moderate nuclear pleomorphism, vesicular chromatin pattern, and prominent nucleoli, sprinkled with small lymphocytes. The tumour cells were strongly diffusely positive for CD21, CD23, and D2-40 immunostaining on cell bock sections, but were negative for CD1a and CD34, supporting the diagnosis of FDCS. Follow-up surgical pathology on the resection showed histopathological features and an immunohistochemical profile consistent with FDCS. 相似文献
89.
Mai Zahran Cigdem Sevim?Bayrak Shereef Elmetwaly Tamar Schlick 《Nucleic acids research》2015,43(19):9474-9488
To address many challenges in RNA structure/function prediction, the characterization of RNA''s modular architectural units is required. Using the RNA-As-Graphs (RAG) database, we have previously explored the existence of secondary structure (2D) submotifs within larger RNA structures. Here we present RAG-3D—a dataset of RNA tertiary (3D) structures and substructures plus a web-based search tool—designed to exploit graph representations of RNAs for the goal of searching for similar 3D structural fragments. The objects in RAG-3D consist of 3D structures translated into 3D graphs, cataloged based on the connectivity between their secondary structure elements. Each graph is additionally described in terms of its subgraph building blocks. The RAG-3D search tool then compares a query RNA 3D structure to those in the database to obtain structurally similar structures and substructures. This comparison reveals conserved 3D RNA features and thus may suggest functional connections. Though RNA search programs based on similarity in sequence, 2D, and/or 3D structural elements are available, our graph-based search tool may be advantageous for illuminating similarities that are not obvious; using motifs rather than sequence space also reduces search times considerably. Ultimately, such substructuring could be useful for RNA 3D structure prediction, structure/function inference and inverse folding. 相似文献
90.
Isadora S. Cohen Carmit Bar Tamar Paz-Elizur Elena Ainbinder Karoline Leopold Niels de?Wind Nicholas Geacintov Zvi Livneh 《Nucleic acids research》2015,43(3):1637-1645
DNA-damage tolerance (DDT) via translesion DNA synthesis (TLS) or homology-dependent repair (HDR) functions to bypass DNA lesions encountered during replication, and is critical for maintaining genome stability. Here, we present piggyBlock, a new chromosomal assay that, using piggyBac transposition of DNA containing a known lesion, measures the division of labor between the two DDT pathways. We show that in the absence of DNA damage response, tolerance of the most common sunlight-induced DNA lesion, TT-CPD, is achieved by TLS in mouse embryo fibroblasts. Meanwhile, BP-G, a major smoke-induced DNA lesion, is bypassed primarily by HDR, providing the first evidence for this mechanism being the main tolerance pathway for a biologically important lesion in a mammalian genome. We also show that, far from being a last-resort strategy as it is sometimes portrayed, TLS operates alongside nucleotide excision repair, handling 40% of TT-CPDs in repair-proficient cells. Finally, DDT acts in mouse embryonic stem cells, exhibiting the same pattern—mutagenic TLS included—despite the risk of propagating mutations along all cell lineages. The new method highlights the importance of HDR, and provides an effective tool for studying DDT in mammalian cells. 相似文献