首页 | 本学科首页   官方微博 | 高级检索  
文章检索
  按 检索   检索词:      
出版年份:   被引次数:   他引次数: 提示:输入*表示无穷大
  收费全文   2296篇
  免费   205篇
  2023年   15篇
  2022年   20篇
  2021年   48篇
  2020年   33篇
  2019年   37篇
  2018年   36篇
  2017年   39篇
  2016年   70篇
  2015年   118篇
  2014年   125篇
  2013年   137篇
  2012年   204篇
  2011年   174篇
  2010年   122篇
  2009年   101篇
  2008年   154篇
  2007年   187篇
  2006年   157篇
  2005年   144篇
  2004年   110篇
  2003年   100篇
  2002年   125篇
  2001年   23篇
  2000年   17篇
  1999年   24篇
  1998年   34篇
  1997年   18篇
  1996年   14篇
  1995年   15篇
  1994年   8篇
  1993年   10篇
  1992年   9篇
  1991年   8篇
  1990年   6篇
  1989年   3篇
  1988年   5篇
  1987年   7篇
  1985年   4篇
  1984年   3篇
  1983年   6篇
  1982年   6篇
  1981年   3篇
  1979年   3篇
  1978年   2篇
  1977年   3篇
  1976年   2篇
  1975年   2篇
  1974年   2篇
  1967年   2篇
  1955年   1篇
排序方式: 共有2501条查询结果,搜索用时 31 毫秒
61.
Many authors have suggested that the negative effects of roads on animals are largely owing to traffic noise. Although suggestive, most past studies of the effects of road noise on wildlife were conducted in the presence of the other confounding effects of roads, such as visual disturbance, collisions and chemical pollution among others. We present, to our knowledge, the first study to experimentally apply traffic noise to a roadless area at a landscape scale—thus avoiding the other confounding aspects of roads present in past studies. We replicated the sound of a roadway at intervals—alternating 4 days of noise on with 4 days off—during the autumn migratory period using a 0.5 km array of speakers within an established stopover site in southern Idaho. We conducted daily bird surveys along our ‘Phantom Road’ and in a nearby control site. We document over a one-quarter decline in bird abundance and almost complete avoidance by some species between noise-on and noise-off periods along the phantom road and no such effects at control sites—suggesting that traffic noise is a major driver of effects of roads on populations of animals.  相似文献   
62.
The ability to detect recent hybridization between dogs and wolves is important for conservation and legal actions, which often require accurate and rapid resolution of ancestry. The availability of a genetic test for dog–wolf hybrids would greatly support federal and legal enforcement efforts, particularly when the individual in question lacks prior ancestry information. We have developed a panel of 100 unlinked ancestry-informative SNP markers that can detect mixed ancestry within up to four generations of dog–wolf hybridization based on simulations of seven genealogical classes constructed following the rules of Mendelian inheritance. We establish 95 % confidence regions around the spatial clustering of each genealogical class using a tertiary plot of allele dosage and heterozygosity. The first- and second-backcrossed-generation hybrids were the most distinct from parental populations, with >90 % correctly assigned to genealogical class. In this article we provide a tool kit with population-level statistical quantification that can detect recent dog–wolf hybridization using a panel of dog–wolf ancestry-informative SNPs with divergent allele frequency distributions.  相似文献   
63.
Understanding the impact of fisheries on the commercial fish stocks requires detailed catch statistics and data on the dynamics of fleet and catch effort, at least before industrial fishing started. Most time-series on the fleet dynamics start after the 1980s, at times when major changes in fleet characteristics had already taken place. In the present paper, the results of the integration of data on fleet size (from 1830), tonnage (from 1842) and engine power (kW, from 1912) of the Belgian sea fisheries fleet are presented. The decrease in fleet size and changes in overall tonnage and engine power since the beginning of the reconstructed time-series, are quantified. The data show that the decrease in fleet size (?85 %) and in overall engine power (?5 %) was compensated by an increase in average tonnage per vessel (×10 increase) and in average engine power per vessel (×6 increase). The overall fishing effort of the fleet expressed as the total number of days spent at sea has decreased by approximately ?84 % between 1938 and 2010, while the average amount of fish landed per day per vessel (1,000 kg in 2008–2010) has at least doubled in the same period. The data reconstruction provides a unique view on the dynamics in the sea fisheries fleet of Belgium over 180 years and the political and social events associated to these changes.  相似文献   
64.
Designed ankyrin repeat proteins (DARPins) are well‐established binding molecules based on a highly stable nonantibody scaffold. Building on 13 crystal structures of DARPin‐target complexes and stability measurements of DARPin mutants, we have generated a new DARPin library containing an extended randomized surface. To counteract the enrichment of unspecific hydrophobic binders during selections against difficult targets containing hydrophobic surfaces such as membrane proteins, the frequency of apolar residues at diversified positions was drastically reduced and substituted by an increased number of tyrosines. Ribosome display selections against two human caspases and membrane transporter AcrB yielded highly enriched pools of unique and strong DARPin binders which were mainly monomeric. We noted a prominent enrichment of tryptophan residues during binder selections. A crystal structure of a representative of this library in complex with caspase‐7 visualizes the key roles of both tryptophans and tyrosines in providing target contacts. These aromatic and polar side chains thus substitute the apolar residues valine, leucine, isoleucine, methionine, and phenylalanine of the original DARPins. Our work describes biophysical and structural analyses required to extend existing binder scaffolds and simplifies an existing protocol for the assembly of highly diverse synthetic binder libraries.  相似文献   
65.
The implications of transitioning to single nucleotide polymorphism (SNPs) from microsatellite markers (MSs) have been investigated in a number of population genetics studies, but the effect of genomic location on the amount of information each type of marker reveals has not been explored in detail. We developed novel SNP markers flanking 1 kb regions of 13 genic (within gene or <1 kb away from gene) and 13 nongenic (>10 kb from annotated gene) MSs in the threespine stickleback genome to obtain comparable data for both types of markers. We analysed patterns of genetic diversity and divergence on various geographic scales after converting the SNP loci within each genomic region into haplotypes. Marker type (SNP haplotype or MS) and location (genic or nongenic) significantly affected most estimates of population diversity and divergence. Between‐lineage divergence was significantly higher in SNP haplotypes (genic and nongenic), however, within‐lineage divergence was similar between marker types. Most divergence and diversity measures were uncorrelated between markers, except for population differentiation which was correlated between MSs and SNP haplotypes (both genic and nongenic). Broad‐scale population structure and assignment were similarly resolved by both marker types, however, only the MSs were able to delimit fine‐scale population structuring, particularly when genic and nongenic markers were combined. These results demonstrate that estimates of genetic variability and differentiation among populations can be strongly influenced by marker type, their genomic location in relation to genes and by the interaction of these two factors. This highlights the importance of having an awareness of the inherent strengths and limitations associated with different molecular tools to select the most appropriate methods for accurately addressing various ecological and evolutionary questions.  相似文献   
66.
Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439.  相似文献   
67.
A prospective study was conducted in client-owned geriatric dogs to evaluate the short-term effects of a test food on serum symmetric dimethylarginine (SDMA) and creatinine (Cr) concentrations. Test food contained functional lipids (fish oil), antioxidants (lipoic acid, vitamins C and E), L-carnitine, botanicals (fruits and vegetables), controlled sodium concentration, and high quality protein sources (high bioavailability and an ideal amino acid composition). Dogs (n = 210) were fed either test food or owner’s-choice foods (non-nutritionally controlled cohort). Dogs were included based on age and body weight: small (6.8 to 11.4 kg) and medium dogs (11.5 to 22.7 kg) were ≥ 9 years, whereas dogs >22.7 kg were ≥ 7 years at baseline. At baseline, all dogs had to have serum Cr concentrations within the reference interval and be free of chronic disease. Renal function biomarkers and urinalysis results at baseline, and after consuming test food or owner’s-choice foods for 3 and 6 months, were evaluated. Only dogs consuming test food showed significant decreases in serum SDMA and Cr concentrations (both P ≤ 0.05) across time. At baseline or during the 6-month feeding trial, 18 dogs (8.6%) had increased serum SDMA, but normal serum Cr, consistent with IRIS Stage 1 chronic kidney disease. This included 9 dogs fed test food and 9 dogs fed owner’s-choice foods. Compared with baseline, after feeding 9 dogs test food for 6 months, serum SDMA decreased in 8 dogs and increased in 1 dog. After feeding 9 dogs owner’s-choice foods for 6 months, serum SDMA decreased in 4 dogs and increased in 4 dogs (remained stable in 1 dog). The decreases in serum SDMA and Cr concentrations were significant (both P = 0.03) only for dogs fed test food. These results suggest that nonazotemic dogs with elevated serum SDMA (early renal insufficiency) when fed a test food designed to promote healthy aging are more likely to demonstrate improved renal function compared with dogs fed owner’s-choice foods.  相似文献   
68.
In 2010 the identities of thousands of anti-Plasmodium compounds were released publicly to facilitate malaria drug development. Understanding these compounds’ mechanisms of action—i.e., the specific molecular targets by which they kill the parasite—would further facilitate the drug development process. Given that kinases are promising anti-malaria targets, we screened ~14,000 cell-active compounds for activity against five different protein kinases. Collections of cell-active compounds from GlaxoSmithKline (the ~13,000-compound Tres Cantos Antimalarial Set, or TCAMS), St. Jude Children’s Research Hospital (260 compounds), and the Medicines for Malaria Venture (the 400-compound Malaria Box) were screened in biochemical assays of Plasmodium falciparum calcium-dependent protein kinases 1 and 4 (CDPK1 and CDPK4), mitogen-associated protein kinase 2 (MAPK2/MAP2), protein kinase 6 (PK6), and protein kinase 7 (PK7). Novel potent inhibitors (IC50 < 1 μM) were discovered for three of the kinases: CDPK1, CDPK4, and PK6. The PK6 inhibitors are the most potent yet discovered for this enzyme and deserve further scrutiny. Additionally, kinome-wide competition assays revealed a compound that inhibits CDPK4 with few effects on ~150 human kinases, and several related compounds that inhibit CDPK1 and CDPK4 yet have limited cytotoxicity to human (HepG2) cells. Our data suggest that inhibiting multiple Plasmodium kinase targets without harming human cells is challenging but feasible.  相似文献   
69.
Establishing nature reserves protects species from land cover conversion and the resulting loss of habitat. Even within a reserve, however, many factors such as fires and defoliating insects still threaten habitat and the survival of species. To address the risk to species survival after reserve establishment, reserve networks can be created that allow some redundancy of species coverage to maximize the expected number of species that survive in the presence of threats. In some regions, however, the threats to species within a reserve may be spatially correlated. As examples, fires, diseases, and pest infestations can spread from a starting point and threaten neighboring parcels’ habitats, in addition to damage caused at the initial location. This paper develops a reserve site selection optimization framework that compares the optimal reserve networks in cases where risks do and do not reflect spatial correlation. By exploring the impact of spatially-correlated risk on reserve networks on a stylized landscape and on an Oregon landscape, this analysis demonstrates an appropriate and feasible method for incorporating such post-reserve establishment risks in the reserve site selection literature as an additional tool to be further developed for future conservation planning.  相似文献   
70.
Although theoretical models have demonstrated that predator–prey population dynamics can depend critically on age (stage) structure and the duration and variability in development times of different life stages, experimental support for this theory is non‐existent. We conducted an experiment with a host–parasitoid system to test the prediction that increased variability in the development time of the vulnerable host stage can promote interaction stability. Host–parasitoid microcosms were subjected to two treatments: Normal and High variance in the duration of the vulnerable host stage. In control and Normal‐variance microcosms, hosts and parasitoids exhibited distinct population cycles. In contrast, insect abundances were 18–24% less variable in High‐ than Normal‐variance microcosms. More significantly, periodicity in host–parasitoid population dynamics disappeared in the High‐variance microcosms. Simulation models confirmed that stability in High‐variance microcosms was sufficient to prevent extinction. We conclude that developmental variability is critical to predator–prey population dynamics and could be exploited in pest‐management programs.  相似文献   
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号