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101.
Connolly SA Landsburg DJ Carfi A Whitbeck JC Zuo Y Wiley DC Cohen GH Eisenberg RJ 《Journal of virology》2005,79(2):1282-1295
Four glycoproteins (gD, gB, gH, and gL) are essential for herpes simplex virus (HSV) entry into cells. An early step of fusion requires gD to bind one of several receptors, such as nectin-1 or herpesvirus entry mediator (HVEM). We hypothesize that a conformational change in gD occurs upon receptor binding that triggers the other glycoproteins to mediate fusion. Comparison of the crystal structures of gD alone and gD bound to HVEM reveals that upon HVEM binding, the gD N terminus transitions from a flexible stretch of residues to a hairpin loop. To address the contribution of this transition to the ability of gD to trigger fusion, we attempted to "lock" the gD N terminus into a looped conformation by engineering a disulfide bond at its N and C termini. The resulting mutant (gD-A3C/Y38C) failed to trigger fusion in the absence of receptor, suggesting that formation of the loop is not the sole fusion trigger. Unexpectedly, although gD-A3C/Y38C bound HVEM, it failed to bind nectin-1. This was due to the key role played by Y38 in interacting with nectin-1. Since tyrosines are often "hot spot" residues at the center of protein-protein interfaces, we mutated residues that surround Y38 on the same face of gD and tested their binding and functional properties. Our results suggest that this region of gD is important for nectin-1 interaction and is distinct from but partially overlaps the site of HVEM binding. Unique gD mutants with altered receptor usage generated in this study may help dissect the roles played by various HSV receptors during infection. 相似文献
102.
Catch and discards from experimental trawl and longline fishing in the deep water of the Rockall Trough 总被引:1,自引:0,他引:1
Comparative bottom trawl and longline surveys were carried out on two chartered commercial fishing vessels in the deep waters (350-1300 m) of the Rockall Trough, an area subjected to heavy commercial exploitation. The species composition, catch rates and length distributions from each survey were very different and reflected the fundamental difference in the two types of fishing operations. Bottom-trawled catches produced greater species diversity and higher discard rates. Longline catches produced larger specimens of teleost fish and were dominated by squalid shark. Trawl discards, expressed as kgs of discards per tonne of roundnose grenadier Coryphaenoides rupestris landed, were calculated for a broad range of the most abundant species taken in the catch. First estimates of total international discarding from deep-water trawling operations in the Rockall Trough area (7530 tonnes; 26.5 million individuals) were made by raising the discard rates using international grenadier landings for 1995. The outlook for the continued exploitation of the deep-water fish resource in the Rockall Trough and possible management options are discussed. 相似文献
103.
Jianhua Ren Yuan Tian Ekram Hossain Joshua S. Ho Yadwinder S. Mann Yuntao Zhang Michael D. Browne Michael D. Connolly Ronald N. Zuckermann 《Biopolymers》2020,111(7):e23358
Peptoids belong to a class of sequence-controlled polymers comprising of N-alkylglycine. This study focuses on using tandem mass spectrometry techniques to characterize the fragmentation patterns of a set of singly and doubly protonated peptoids consisting of one basic residue placed at different positions. The singly protonated peptoids fragment by producing predominately high-abundant C-terminal ions called Y-ions and low-abundant N-terminal ions called B-ions. Computational studies suggest that the proton affinity (PA) of the C-terminal fragments is generally higher than that of the N-terminal fragments, and the PA of the former increases as the fragments are elongated. The B-ions are likely formed upon dissociating the proton-activated amide bonds via an oxazolone structure, and the Y-ions are produced subsequently by abstracting a proton from the newly formed B-ions, which is energetically favored. The doubly protonated peptoids prefer to fragment closest to either the N- or the C-terminus and produce corresponding B/Y-ion pairs. The basic residue seems to dictate the preferred fragmentation site, which may be the result of minimizing the repulsion between the two charges. Water and terminal neutral losses are a facile process accompanying the peptoid fragmentation in both charge states. The patterns appear to be highly influenced by the location of the basic residue. 相似文献
104.
Siegfried Huneck Joseph D. Connolly Leslie J. Harrison Robert S.I. Joseph Thomas Pócs 《Phytochemistry》1984,23(10):2396-2397
Extraction of the liverwort Plagiochila rutilans afforded 1-(3,4-dihydroxy-5-methoxyphenyl)3-methylbut-2-ene, the structure of which was confirmed by synthesis. 相似文献
105.
Komguem J Meli AL Manfouo RN Lontsi D Ngounou FN Kuete V Kamdem HW Tane P Ngadjui BT Sondengam BL Connolly JD 《Phytochemistry》2005,66(14):1713-1717
Two new xanthones, smeathxanthone A (1) (2-(3,7-dimethyl-2,6-octadienyl)-1,3,5,8-tetrahydroxyxanthone) and smeathxanthone B (2) (5,7,10-trihydroxy-2-methyl-2-(4-methylpent-3-enyl)[2H, 6H]pyrano[3,2-b]xanthen-6-one), have been isolated from the stem bark of Garcinia smeathmannii, and their structures elucidated on the basis of 1D and 2D NMR experiments. 1,3,5-Trihydroxyxanthone and 1,5-dihydroxyxanthone were also obtained. The compounds showed only modest activity against a range of bacteria and yeasts. 相似文献
106.
A microcosm-based approach was used to study impacts of plant and chemical factors on the fungal community structure of an upland acidic grassland soil. Seven plant species typical of both unimproved and fertilized grasslands were either left unamended or treated with lime, nitrogen or lime plus nitrogen. Fungal community structure was assessed by a molecular approach, fungal automated ribosomal intergenic spacer analysis (FARISA), while fungal biomass was estimated by measuring soil ergosterol content. Addition of nitrogen (with or without lime) had the largest effect, decreasing soil pH, fungal biomass and fungal ribotype number, but there was little corresponding change in fungal community structure. Although different plant species were associated with some changes in fungal biomass, this did not result in significant differences in fungal community structure between plant species. Addition of lime alone caused no changes in fungal biomass, ribotype number or community structure. Overall, fungal community structure appeared to be more significantly affected through interactions between plant species and chemical treatments, as opposed to being directly affected by changes in individual improvement factors. These results were in contrast to those found for the bacterial communities of the same soils, which changed substantially in response to chemical (lime and nitrogen) additions. 相似文献
107.
Background
The Darlington and Northallerton Asthma Study is an observational cohort study started in 1983. At that time little was published about long term outcome in asthma and the contribution of change in reversible disease or airway remodelling to any excess deterioration in function. The study design included regular review of overall and fixed function lung. We report the trends over fifteen years.Methods
All asthmatics attending secondary care in 1983, 1988 and 1993 were recruited. Pulmonary function was recorded at attendance and potential best function estimated according to protocol. Rate of decline was calculated over each 5-year period and by linear regression analysis in those seen every time. The influence of potential explanatory variables on this decline was explored.Results
1724 satisfactory 5-year measurements were obtained in 912 subjects and in 200 subjects on all occasions. Overall rate of decline (ml/year (95%CI)) calculated from 5-year periods was FEV1 ♂41.0 (34.7–47.3), ♀28.9 (23.2–34.6) and best FVC ♂63.1 (55.1–71.2)ml/year, ♀45.8 (40.0–51.6).The principal association was with age. A dominant cubic factor suggested fluctuations in the rate of change in middle life with less rapid decline in youth and more rapid decline in the elderly. Rapid decline was possibly associated with short duration. Treatment step did not predict rate of deterioration.Conclusions
Function declined non-linearly and more rapidly than predicted from normal subjects. It reports for the first time a cubic relationship between age and pulmonary function. This should be taken into account when interpreting other articles reporting change in function over time. 相似文献108.
An evaluation, comparison, and accurate benchmarking of several publicly available MS/MS search algorithms: sensitivity and specificity analysis 总被引:1,自引:0,他引:1
Kapp EA Schütz F Connolly LM Chakel JA Meza JE Miller CA Fenyo D Eng JK Adkins JN Omenn GS Simpson RJ 《Proteomics》2005,5(13):3475-3490
MS/MS and associated database search algorithms are essential proteomic tools for identifying peptides. Due to their widespread use, it is now time to perform a systematic analysis of the various algorithms currently in use. Using blood specimens used in the HUPO Plasma Proteome Project, we have evaluated five search algorithms with respect to their sensitivity and specificity, and have also accurately benchmarked them based on specified false-positive (FP) rates. Spectrum Mill and SEQUEST performed well in terms of sensitivity, but were inferior to MASCOT, X!Tandem, and Sonar in terms of specificity. Overall, MASCOT, a probabilistic search algorithm, correctly identified most peptides based on a specified FP rate. The rescoring algorithm, PeptideProphet, enhanced the overall performance of the SEQUEST algorithm, as well as provided predictable FP error rates. Ideally, score thresholds should be calculated for each peptide spectrum or minimally, derived from a reversed-sequence search as demonstrated in this study based on a validated data set. The availability of open-source search algorithms, such as X!Tandem, makes it feasible to further improve the validation process (manual or automatic) on the basis of "consensus scoring", i.e., the use of multiple (at least two) search algorithms to reduce the number of FPs. complement. 相似文献
109.
Orsini MJ Nesmelova I Young HC Hargittai B Beavers MP Liu J Connolly PJ Middleton SA Mayo KH 《The Journal of biological chemistry》2005,280(9):8134-8142
Nociceptin, a 17 amino acid opioid-like peptide that has an inhibitory effect on synaptic transmission in the nervous system, is involved in learning, memory, attention, and emotion and is also implicated in the perception of pain and visual, auditory, and olfactory functions. In this study, we investigated the NMR solution structure of nociceptin in membrane-like environments (trifluoroethanol and SDS micelles) and found it to have a relatively stable helix conformation from residues 4-17 with functionally important N-terminal residues being folded aperidoically on top of the helix. In functional assays for receptor binding and calcium flux, alanine-scanning variants of nociceptin indicated that functionally important residues generally followed helix periodicity, consistent with the NMR structural model. Structure-activity relationships allowed identification of pharmacophore sites that were used in small molecule data base searches, affording hits with demonstrated nociceptin receptor binding affinities. 相似文献
110.
Cadden IS Johnston BT Connolly R Gates D Tsujimoto Y Eguchi Y McGinty A 《Biochemical and biophysical research communications》2005,326(2):442-448
INTRODUCTION: In addition to its role in apoptosis suppression, Bcl-2 has been reported to be co-expressed with neuroendocrine markers in several tissues, leading to speculation that this oncoprotein may promote neuroendocrine differentiation. AIM: This study investigated whether Bcl-2 modulated neuroendocrine biopeptide expression. METHODS: Levels of chromogranin A, neurone specific enolase, protein gene peptide 9.5, pancreatic polypeptide, and the chromogranin-derived peptides, intervening peptide and vasostatin-1 were examined by immunocytochemistry in rat phaeochromocytoma (PC12) cell lines genetically engineered to over-express Bcl-2 and their mock-transfected controls. Intensity of fluorescence was graded using a semi-quantitative scale from (-) indicating negative expression to (+++) indicating intense positivity. RESULTS: Mann-Whitney U analysis indicated that no significant differences in expression existed between control and Bcl2 over-expressing cell lines for any of the six peptides examined. CONCLUSIONS: The results of this study do not support the hypothesis that Bcl-2 promotes the acquisition of a neuroendocrine phenotype. 相似文献