全文获取类型
收费全文 | 31471篇 |
免费 | 2673篇 |
国内免费 | 120篇 |
出版年
2022年 | 199篇 |
2021年 | 458篇 |
2020年 | 300篇 |
2019年 | 432篇 |
2018年 | 505篇 |
2017年 | 413篇 |
2016年 | 665篇 |
2015年 | 1060篇 |
2014年 | 1156篇 |
2013年 | 1601篇 |
2012年 | 1820篇 |
2011年 | 1665篇 |
2010年 | 1225篇 |
2009年 | 962篇 |
2008年 | 1459篇 |
2007年 | 1417篇 |
2006年 | 1341篇 |
2005年 | 1199篇 |
2004年 | 1203篇 |
2003年 | 1125篇 |
2002年 | 1218篇 |
2001年 | 999篇 |
2000年 | 899篇 |
1999年 | 818篇 |
1998年 | 409篇 |
1997年 | 400篇 |
1996年 | 317篇 |
1995年 | 318篇 |
1994年 | 237篇 |
1993年 | 288篇 |
1992年 | 555篇 |
1991年 | 518篇 |
1990年 | 484篇 |
1989年 | 438篇 |
1988年 | 356篇 |
1987年 | 353篇 |
1986年 | 330篇 |
1985年 | 379篇 |
1984年 | 353篇 |
1983年 | 314篇 |
1982年 | 227篇 |
1981年 | 232篇 |
1980年 | 208篇 |
1979年 | 282篇 |
1978年 | 243篇 |
1977年 | 267篇 |
1976年 | 254篇 |
1975年 | 250篇 |
1974年 | 246篇 |
1973年 | 234篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
71.
Kathryn S. Evans Janneke Wit Lewis Stevens Steffen R. Hahnel Briana Rodriguez Grace Park Mostafa Zamanian Shannon C. Brady Ellen Chao Katherine Introcaso Robyn E. Tanny Erik C. Andersen 《PLoS pathogens》2021,17(3)
Parasitic nematodes cause a massive worldwide burden on human health along with a loss of livestock and agriculture productivity. Anthelmintics have been widely successful in treating parasitic nematodes. However, resistance is increasing, and little is known about the molecular and genetic causes of resistance for most of these drugs. The free-living roundworm Caenorhabditis elegans provides a tractable model to identify genes that underlie resistance. Unlike parasitic nematodes, C. elegans is easy to maintain in the laboratory, has a complete and well annotated genome, and has many genetic tools. Using a combination of wild isolates and a panel of recombinant inbred lines constructed from crosses of two genetically and phenotypically divergent strains, we identified three genomic regions on chromosome V that underlie natural differences in response to the macrocyclic lactone (ML) abamectin. One locus was identified previously and encodes an alpha subunit of a glutamate-gated chloride channel (glc-1). Here, we validate and narrow two novel loci using near-isogenic lines. Additionally, we generate a list of prioritized candidate genes identified in C. elegans and in the parasite Haemonchus contortus by comparison of ML resistance loci. These genes could represent previously unidentified resistance genes shared across nematode species and should be evaluated in the future. Our work highlights the advantages of using C. elegans as a model to better understand ML resistance in parasitic nematodes. 相似文献
72.
Yi-Shiang Huang Virginie Bertrand Dimitriya Bozukova Christophe Pagnoulle Christine Labrugère Edwin De Pauw Marie-Claire De Pauw-Gillet Marie-Christine Durrieu 《PloS one》2014,9(12)
Posterior Capsular Opacification (PCO) is the capsule fibrosis developed on implanted IntraOcular Lens (IOL) by the de-differentiation of Lens Epithelial Cells (LECs) undergoing Epithelial Mesenchymal Transition (EMT). Literature has shown that the incidence of PCO is multifactorial including the patient''s age or disease, surgical technique, and IOL design and material. Reports comparing hydrophilic and hydrophobic acrylic IOLs have shown that the former has more severe PCO. On the other hand, we have previously demonstrated that the adhesion of LECs is favored on hydrophobic compared to hydrophilic materials. By combining these two facts and contemporary knowledge in PCO development via the EMT pathway, we propose a biomimetically inspired strategy to promote LEC adhesion without de-differentiation to reduce the risk of PCO development. By surface grafting of a cell adhesion molecule (RGD peptide) onto the conventional hydrophilic acrylic IOL material, the surface-functionalized IOL can be used to reconstitute a capsule-LEC-IOL sandwich structure, which has been considered to prevent PCO formation in literature. Our results show that the innovative biomaterial improves LEC adhesion, while also exhibiting similar optical (light transmittance, optical bench) and mechanical (haptic compression force, IOL injection force) properties compared to the starting material. In addition, compared to the hydrophobic IOL material, our bioactive biomaterial exhibits similar abilities in LEC adhesion, morphology maintenance, and EMT biomarker expression, which is the crucial pathway to induce PCO. The in vitro assays suggest that this biomaterial has the potential to reduce the risk factor of PCO development. 相似文献
73.
Mirjam Frischknecht Vidhya Jagannathan Philippe Plattet Markus Neuditschko Heidi Signer-Hasler Iris Bachmann Alicja Pacholewska Cord Dr?gemüller Elisabeth Dietschi Christine Flury Stefan Rieder Tosso Leeb 《PloS one》2015,10(10)
The identification of quantitative trait loci (QTL) such as height and their underlying causative variants is still challenging and often requires large sample sizes. In humans hundreds of loci with small effects control the heritable portion of height variability. In domestic animals, typically only a few loci with comparatively large effects explain a major fraction of the heritability. We investigated height at withers in Shetland ponies and mapped a QTL to ECA 6 by genome-wide association (GWAS) using a small cohort of only 48 animals and the Illumina equine SNP70 BeadChip. Fine-mapping revealed a shared haplotype block of 793 kb in small Shetland ponies. The HMGA2 gene, known to be associated with height in horses and many other species, was located in the associated haplotype. After closing a gap in the equine reference genome we identified a non-synonymous variant in the first exon of HMGA2 in small Shetland ponies. The variant was predicted to affect the functionally important first AT-hook DNA binding domain of the HMGA2 protein (c.83G>A; p.G28E). We assessed the functional impact and found impaired DNA binding of a peptide with the mutant sequence in an electrophoretic mobility shift assay. This suggests that the HMGA2 variant also affects DNA binding in vivo and thus leads to reduced growth and a smaller stature in Shetland ponies. The identified HMGA2 variant also segregates in several other pony breeds but was not found in regular-sized horse breeds. We therefore conclude that we identified a quantitative trait nucleotide for height in horses. 相似文献
74.
75.
Paolo d’Errico Marina Boido Antonio Piras Valeria Valsecchi Elena De Amicis Denise Locatelli Silvia Capra Francesco Vagni Alessandro Vercelli Giorgio Battaglia 《PloS one》2013,8(12)
Loss of the survival motor neuron gene (SMN1) is responsible for spinal muscular atrophy (SMA), the most common inherited cause of infant mortality. Even though the SMA phenotype is traditionally considered as related to spinal motor neuron loss, it remains debated whether the specific targeting of motor neurons could represent the best therapeutic option for the disease. We here investigated, using stereological quantification methods, the spinal cord and cerebral motor cortex of ∆7 SMA mice during development, to verify extent and selectivity of motor neuron loss. We found progressive post-natal loss of spinal motor neurons, already at pre-symptomatic stages, and a higher vulnerability of motor neurons innervating proximal and axial muscles. Larger motor neurons decreased in the course of disease, either for selective loss or specific developmental impairment. We also found a selective reduction of layer V pyramidal neurons associated with layer V gliosis in the cerebral motor cortex. Our data indicate that in the ∆7 SMA model SMN loss is critical for the spinal cord, particularly for specific motor neuron pools. Neuronal loss, however, is not selective for lower motor neurons. These data further suggest that SMA pathogenesis is likely more complex than previously anticipated. The better knowledge of SMA models might be instrumental in shaping better therapeutic options for affected patients. 相似文献
76.
77.
L Missiaen J B Parys A F Weidema H Sipma S Vanlingen P De Smet G Callewaert H De Smedt 《The Journal of biological chemistry》1999,274(20):13748-13751
Calmodulin inhibits inositol 1,4,5-trisphosphate (IP3) binding to the IP3 receptor in both a Ca2+-dependent and a Ca2+-independent way. Because there are no functional data on the modulation of the IP3-induced Ca2+ release by calmodulin at various Ca2+ concentrations, we have studied how cytosolic Ca2+ and Sr2+ interfere with the effects of calmodulin on the IP3-induced Ca2+ release in permeabilized A7r5 cells. We now report that calmodulin inhibited Ca2+ release through the IP3 receptor with an IC50 of 4.6 microM if the cytosolic Ca2+ concentration was 0.3 microM or higher. This inhibition was particularly pronounced at low IP3 concentrations. In contrast, calmodulin did not affect IP3-induced Ca2+ release if the cytosolic Ca2+ concentration was below 0.3 microM. Calmodulin also inhibited Ca2+ release through the IP3 receptor in the presence of at least 10 microM Sr2+. We conclude that cytosolic Ca2+ or Sr2+ are absolutely required for the calmodulin-induced inhibition of the IP3-induced Ca2+ release and that this dependence represents the formation of the Ca2+/calmodulin or Sr2+/calmodulin complex. 相似文献
78.
Most adult Barbus haasi , at a 1950 m-long site in Vallvidrera creek, were highly sedentary and resided within a home range <20 m (32 m2 ), while a small group were more mobile. On successive sampling occasions, between 52·3 and 64·9% of fish were recaptured in the same 10-m-long section in which they had previously been captured. Movements over long distances were infrequent, and only 5·6% of the fish moved >100 m. The movement pattern of the population was seasonally stable, although the mean distances were slightly greater in summer because of the medium-range movements of a few individuals. Overall, upstream and downstream movements were equally common but a significant downstream movement occurred in spring. The size of the fish did not influence the movement rate. Fish inhabiting those sections of the stream with greater depth, slower current and more cover had a lower movement rate than fish occupying shallower, exposed sections. The restricted movement of B. haasi could increase the survival of fish by increasing the probability of staying in the remaining pools during summer dry-out, and may therefore be of adaptive significance. 相似文献
79.
80.
A dipstick enzyme immunoassay for the rapid detection of Fusarium T-2 toxin in wheat was developed. An Immunodyne ABC membrane was precoated with rabbit anti-mouse immunoglobulins. After the strips were immersed in a solution of monoclonal anti-T-2 toxin antibodies, a direct competitive enzyme immunoassay was performed. This assay included the incubation of the antibody-coated dipsticks in a mixture of sample and T-2 toxin-horseradish peroxidase conjugate. Afterwards, the strips were placed in a chromogen-containing substrate solution (H202-3,3',5,5'-tetramethylbenzidine) for color reaction. The dot color intensity of toxin-positive dipsticks was visually distinguishable from that of the negative control. A portable colorimeter was used to confirm and quantify the visual observations. With coated strips, the tests could be performed in 45 min. The visual detection limit for T-2 toxin in buffer solution was 0.25 ng/ml. Artificially infected wheat samples were extracted with 80% methanol-water. A dilution of the raw extract of 1:8 was sufficient to avoid matrix effects. It was possible to make visually a clear distinction between the negative control and a wheat extract spiked with 12 ng/g. 相似文献