全文获取类型
收费全文 | 7811篇 |
免费 | 824篇 |
国内免费 | 3篇 |
出版年
2023年 | 47篇 |
2022年 | 136篇 |
2021年 | 271篇 |
2020年 | 134篇 |
2019年 | 177篇 |
2018年 | 205篇 |
2017年 | 193篇 |
2016年 | 338篇 |
2015年 | 525篇 |
2014年 | 522篇 |
2013年 | 537篇 |
2012年 | 694篇 |
2011年 | 716篇 |
2010年 | 459篇 |
2009年 | 357篇 |
2008年 | 502篇 |
2007年 | 505篇 |
2006年 | 381篇 |
2005年 | 375篇 |
2004年 | 385篇 |
2003年 | 328篇 |
2002年 | 299篇 |
2001年 | 56篇 |
2000年 | 39篇 |
1999年 | 50篇 |
1998年 | 72篇 |
1997年 | 31篇 |
1996年 | 44篇 |
1995年 | 25篇 |
1994年 | 23篇 |
1993年 | 16篇 |
1992年 | 16篇 |
1991年 | 16篇 |
1990年 | 13篇 |
1989年 | 8篇 |
1988年 | 3篇 |
1987年 | 5篇 |
1986年 | 8篇 |
1985年 | 11篇 |
1984年 | 17篇 |
1983年 | 8篇 |
1982年 | 9篇 |
1981年 | 21篇 |
1980年 | 13篇 |
1979年 | 8篇 |
1978年 | 10篇 |
1977年 | 6篇 |
1976年 | 5篇 |
1975年 | 3篇 |
1968年 | 3篇 |
排序方式: 共有8638条查询结果,搜索用时 15 毫秒
161.
Antimicrobial peptides are an important component of innate immunity and have generated considerable interest as a new potential class of natural antibiotics. The biological activity of antimicrobial peptides is strongly influenced by peptide–membrane interactions. Human Neutrophil Peptide 1 (HNP-1) is a 30 aminoacid peptide, belonging to the class of α-defensins. Many biophysical studies have been performed on this peptide to define its mechanism of action. Combining spectroscopic and thermodynamic analysis, insights on the interaction of the α-defensin with POPE:POPG:CL negative charged bilayers are given. The binding states of the peptide below and above the threshold concentration have been analyzed showing that the interaction with lipid bilayers is dependent by peptide concentration. These novel results that indicate how affinity and biological activities of natural antibiotics are depending by their concentration, might open new way of investigation of the antimicrobial mode of action. 相似文献
162.
Karin Chen Emily?M. Coonrod Attila Kumánovics Zechariah F. Franks Jacob?D. Durtschi Rebecca?L. Margraf Wilfred Wu Nahla?M. Heikal Nancy?H. Augustine Perry?G. Ridge Harry?R. Hill Lynn?B. Jorde Andrew?S. Weyrich Guy?A. Zimmerman Adi?V. Gundlapalli John?F. Bohnsack Karl?V. Voelkerding 《American journal of human genetics》2013,93(5):812-824
Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by antibody deficiency, poor humoral response to antigens, and recurrent infections. To investigate the molecular cause of CVID, we carried out exome sequence analysis of a family diagnosed with CVID and identified a heterozygous frameshift mutation, c.2564delA (p.Lys855Serfs∗7), in NFKB2 affecting the C terminus of NF-κB2 (also known as p100/p52 or p100/p49). Subsequent screening of NFKB2 in 33 unrelated CVID-affected individuals uncovered a second heterozygous nonsense mutation, c.2557C>T (p.Arg853∗), in one simplex case. Affected individuals in both families presented with an unusual combination of childhood-onset hypogammaglobulinemia with recurrent infections, autoimmune features, and adrenal insufficiency. NF-κB2 is the principal protein involved in the noncanonical NF-κB pathway, is evolutionarily conserved, and functions in peripheral lymphoid organ development, B cell development, and antibody production. In addition, Nfkb2 mouse models demonstrate a CVID-like phenotype with hypogammaglobulinemia and poor humoral response to antigens. Immunoblot analysis and immunofluorescence microscopy of transformed B cells from affected individuals show that the NFKB2 mutations affect phosphorylation and proteasomal processing of p100 and, ultimately, p52 nuclear translocation. These findings describe germline mutations in NFKB2 and establish the noncanonical NF-κB signaling pathway as a genetic etiology for this primary immunodeficiency syndrome. 相似文献
163.
Kerem Teralı Rebecca L. Beavil Richard W. Pickersgill Mark van der Giezen 《Biochemical and biophysical research communications》2013
Small inorganic assemblies of alternating ferrous/ferric iron and sulphide ions, so-called iron–sulphur (Fe–S) clusters, are possibly nature’s most ancient prosthetic groups. One of the early actors in Fe–S cluster biosynthesis is a protein complex composed of a cysteine desulphurase, Nfs1, and its functional binding partner, Isd11. Although the essential function of Nfs1·Isd11 in the liberation of elemental sulphur from free cysteine is well established, little is known about its structure. Here, we provide evidence that shows Isd11 has a profound effect on the oligomeric state of Nfs1. 相似文献
164.
Martha M. Muñoz Nicholas G. Crawford Thomas J. McGreevy Jr Nicholas J. Messana Rebecca D. Tarvin Liam J. Revell Rosanne M. Zandvliet Juanita M. Hopwood Elbert Mock André L. Schneider Christopher J. Schneider 《Molecular ecology》2013,22(10):2668-2682
Adaptive divergence in coloration is expected to produce reproductive isolation in species that use colourful signals in mate choice and species recognition. Indeed, many adaptive radiations are characterized by differentiation in colourful signals, suggesting that divergent selection acting on coloration may be an important component of speciation. Populations in the Anolis marmoratus species complex from the Caribbean island of Guadeloupe display striking divergence in the colour and pattern of adult males that occurs over small geographic distances, suggesting strong divergent selection. Here we test the hypothesis that divergence in coloration results in reduced gene flow among populations. We quantify variation in adult male coloration across a habitat gradient between mesic and xeric habitats, use a multilocus coalescent approach to infer historical demographic parameters of divergence, and examine gene flow and population structure using microsatellite variation. We find that colour variation evolved without geographic isolation and in the face of gene flow, consistent with strong divergent selection and that both ecological and sexual selection are implicated. However, we find no significant differentiation at microsatellite loci across populations, suggesting little reproductive isolation and high levels of contemporary gene exchange. Strong divergent selection on loci affecting coloration probably maintains clinal phenotypic variation despite high gene flow at neutral loci, supporting the notion of a porous genome in which adaptive portions of the genome remain fixed whereas neutral portions are homogenized by gene flow and recombination. We discuss the impact of these findings for studies of colour evolution and ecological speciation. 相似文献
165.
Noboru Tomiya Juliette G. Jardim Jennifer Hou Rebecca Pastrana-Mena Rhoel R. Dinglasan Yuan C. Lee 《Bioorganic & medicinal chemistry》2013,21(17):5275-5281
We have synthesized poly-γ-glutamic acid (PGA) modified with a synthetic trivalent glyco-ligand (TriGalNAc) for the hepatocyte asialoglycoprotein receptor (ASGP-R). We investigated in vivo distribution of unmodified PGA and TriGalNAc-modified PGA (TriGalNAc-PGA) in mice after intravenous injection. Most of unmodified PGA administered was transported to the bladder over 20–80 min, suggesting a rapid excretion of unmodified PGA into urine. In contrast, TriGalNAc-PGA was found exclusively in the liver over the same period of time. We further synthesized TriGalNAc-PGA–primaquine conjugate (TriGalNAc-PGA–PQ), and investigated binding, uptake, and catabolism of the conjugate by rat hepatocytes. Our studies indicated that approximately 250 ng per million cells of the conjugate bound to one million rat hepatocytes at 0 °C, and approximately 2 μg per million cells of the conjugate was taken up over 7 h incubation at 37 °C. Furthermore, our results suggested that TriGalNAc-PGA–PQ was almost completely degraded over 24 h, and small degradation products were secreted into cell culture medium.The results described in this report suggest that the TriGalNAc ligand can serve as an excellent targeting device for delivery of PGA-conjugates to the liver hepatocytes, and rat hepatocytes possess sufficient capacity to digest PGA even modified with other substituents. 相似文献
166.
167.
Daniel J. Peart Richard J. Kirk Leigh A. Madden Jason C. Siegler Rebecca V. Vince 《Amino acids》2013,44(3):903-910
The aim of this study was to observe the intracellular heat shock protein 72 (HSP72) and heme oxygenase-1 (HSP32) response to prolonged interval cycling following the ingestion of carbohydrates (CHO) and sodium bicarbonate (NaHCO3). Six recreationally active males (mean ± SD; age 23.2 ± 2.9 years, height 179.5 ± 5.5 cm, body mass 76.5 ± 6.8 kg, and peak power output 315 ± 36 W) volunteered to complete a 90 min interval cycling exercise on four occasions. The trials were completed in a random and blinded manner following ingestion of either: placebo and an artificial sweetener (P–P), NaHCO3 and sweetener (B–P), placebo and CHO (P–CHO), and NaHCO3 and CHO (B–CHO). Both HSP72 and HSP32 were significantly increased in monocytes and lymphocytes from 45 min post-exercise (p ≤ 0.039), with strong relationships between both cell types (HSP72, r = 0.83; HSP32, r = 0.89). Exogenous CHO had no influence on either HSP72 or HSP32, but the ingestion of NaHCO3 significantly attenuated HSP32 in monocytes and lymphocytes (p ≤ 0.042). In conclusion, the intracellular stress protein response to 90 min interval exercise is closely related in monocytes and lymphocytes, and HSP32 appears to be attenuated with a pre-exercise alkalosis. 相似文献
168.
169.
Rebecca C. Jones Dorothy A. Steane Martyn Lavery René E. Vaillancourt Brad M. Potts 《Ecology and evolution》2013,3(1):1-17
Forest trees frequently form species complexes, complicating taxonomic classification and gene pool management. This is certainly the case in Eucalyptus, and well exemplified by the Eucalyptus globulus complex. This ecologically and economically significant complex comprises four taxa (sspp. bicostata, globulus, maidenii, pseudoglobulus) that are geographically and morphologically distinct, but linked by extensive “intergrade” populations. To resolve their genetic affinities, nine microsatellites were used to genotype 1200 trees from throughout the natural range of the complex in Australia, representing 33 morphological core and intergrade populations. There was significant spatial genetic structure (FST = 0.10), but variation was continuous. High genetic diversity in southern ssp. maidenii indicates that this region is the center of origin. Genetic diversity decreases and population differentiation increases with distance from this area, suggesting that drift is a major evolutionary process. Many of the intergrade populations, along with other populations morphologically classified as ssp. pseudoglobulus or ssp. globulus, belong to a “cryptic genetic entity” that is genetically and geographically intermediate between core ssp. bicostata, ssp. maidenii, and ssp. globulus. Geography, rather than morphology, therefore, is the best predictor of overall genetic affinities within the complex and should be used to classify germplasm into management units for conservation and breeding purposes. 相似文献
170.
Grace?S?Tan Rebecca?Lewandowski Michael?J?Mallory Randy?Strich Katrina?F?CooperEmail author 《Cell division》2013,8(1):9