全文获取类型
收费全文 | 4926篇 |
免费 | 367篇 |
专业分类
5293篇 |
出版年
2023年 | 26篇 |
2022年 | 34篇 |
2021年 | 53篇 |
2020年 | 47篇 |
2019年 | 71篇 |
2018年 | 141篇 |
2017年 | 109篇 |
2016年 | 175篇 |
2015年 | 257篇 |
2014年 | 210篇 |
2013年 | 357篇 |
2012年 | 373篇 |
2011年 | 353篇 |
2010年 | 221篇 |
2009年 | 197篇 |
2008年 | 271篇 |
2007年 | 255篇 |
2006年 | 225篇 |
2005年 | 262篇 |
2004年 | 203篇 |
2003年 | 178篇 |
2002年 | 174篇 |
2001年 | 122篇 |
2000年 | 138篇 |
1999年 | 92篇 |
1998年 | 30篇 |
1997年 | 26篇 |
1996年 | 23篇 |
1995年 | 32篇 |
1994年 | 20篇 |
1993年 | 15篇 |
1992年 | 60篇 |
1991年 | 45篇 |
1990年 | 40篇 |
1989年 | 33篇 |
1988年 | 32篇 |
1987年 | 34篇 |
1986年 | 34篇 |
1985年 | 34篇 |
1984年 | 20篇 |
1983年 | 18篇 |
1980年 | 16篇 |
1977年 | 14篇 |
1976年 | 16篇 |
1974年 | 14篇 |
1973年 | 20篇 |
1972年 | 21篇 |
1970年 | 17篇 |
1968年 | 13篇 |
1965年 | 20篇 |
排序方式: 共有5293条查询结果,搜索用时 9 毫秒
921.
Pevarello P Fancelli D Vulpetti A Amici R Villa M Pittalà V Vianello P Cameron A Ciomei M Mercurio C Bischoff JR Roletto F Varasi M Brasca MG 《Bioorganic & medicinal chemistry letters》2006,16(4):1084-1090
We have recently reported about a new class of Aurora-A inhibitors based on a bicyclic tetrahydropyrrolo[3,4-c]pyrazole scaffold. Here we describe the synthesis and early expansion of CDK2/cyclin A-E inhibitors belonging to the same chemical class. Synthesis of the compounds was accomplished using a solution-phase protocol amenable to rapid parallel expansion. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit CDK2-mediated tumor cell proliferation have been obtained. 相似文献
922.
Soldà T Garbi N Hämmerling GJ Molinari M 《The Journal of biological chemistry》2006,281(10):6219-6226
Members of the protein-disulfide isomerase superfamily catalyze the formation of intra- and intermolecular disulfide bonds, a rate-limiting step of protein folding in the endoplasmic reticulum (ER). Here we compared maturation of one obligate and two facultative calnexin substrates in cells with and without ERp57, the calnexin-associated, glycoprotein-specific oxidoreductase. ERp57 deletion did not prevent the formation of disulfide bonds during co-translational translocation of nascent glycopolypeptides in the ER. It affected, however, the post-translational phases of oxidative influenza virus hemagglutinin (HA) folding, resulting in significant loss of folding efficiency for this obligate calnexin substrate. Without ERp57, HA also showed reduced capacity to recover from an artificially induced aberrant conformation, thus revealing a crucial role of ERp57 during post-translational reshuffling to the native set of HA disulfides. ERp57 deletion did not affect maturation of the model facultative calnexin substrates E1 and p62 (and of most cellular proteins, as shown by lack of induction of ER stress). ERp72 was identified as one of the ER-resident oxidoreductases associating with the orphan ERp57 substrates to maintain their folding competence. 相似文献
923.
924.
Pasquale Emanuele Scopelliti Antonio Borgonovo Marco Indrieri Luca Giorgetti Gero Bongiorno Roberta Carbone Alessandro Podestà Paolo Milani 《PloS one》2010,5(7)
Background
Protein adsorption is the first of a complex series of events that regulates many phenomena at the nano-bio interface, e.g. cell adhesion and differentiation, in vivo inflammatory responses and protein crystallization. A quantitative understanding of how nanoscale morphology influences protein adsorption is strategic for providing insight into all of these processes, however this understanding has been lacking until now.Methodology/Principal Findings
Here we introduce novel methods for quantitative high-throughput characterization of protein-surface interaction and we apply them in an integrated experimental strategy, to study the adsorption of a panel of proteins on nanostructured surfaces. We show that the increase of nanoscale roughness (from 15 nm to 30 nm) induces a decrease of protein binding affinity (≤90%) and a relevant increase in adsorbed proteins (≤500%) beyond the corresponding increase of specific area. We demonstrate that these effects are caused by protein nucleation on the surface, which is promoted by surface nanoscale pores.Conclusions/Significance
These results show that the adsorption of proteins depends significantly on surface nanostructure and that the relevant morphological parameter regulating the protein adsorption process is the nanometric pore shape. These new findings improve our understanding of the role of nanostructures as a biomaterial design parameter and they have important implications for the general understanding of cell behavior on nanostructured surfaces. 相似文献925.
Giribet G Rambla M Carranza S Baguñà J Riutort M Ribera C 《Molecular phylogenetics and evolution》1999,11(2):296-307
The phylogenetic relationships among the main evolutionary lines of the arachnid order Opiliones were investigated by means of molecular (complete 18S rDNA and the D3 region of the 28S rDNA genes) and morphological data sets. Equally and differentially weighted parsimony analyses of independent and combined data sets provide evidence for the monophyly of the Opiliones. In all the analyses, the internal relationships of the group coincide in the monophyly of the following main groups: Cyphophthalmi, Eupnoi Palpatores, Dyspnoi Palpatores, and Laniatores. The Cyphophthalmi are monophyletic and sister to a clade that includes all the remaining opilionid taxa (=Phalangida). Within the Phalangida the most supported hypothesis suggests that Palpatores are paraphyletic, as follows: (Eupnoi (Dyspnoi + Laniatores)), but the alternative hypothesis (Laniatores (Eupnoi + Dyspnoi)) is more parsimonious in some molecular data analyses. Relationships within the four main clades are also addressed. Evolution of some morphological characters is discussed, and plesiomorphic states of these characters are evaluated using molecular data outgroup polarization. Finally, Martens' hypothesis of opilionid evolution is assessed in relation to our results. 相似文献
926.
Mazzucco S Matà S Vergelli M Fioresi R Nardi E Mazzanti B Chelli M Lolli F Ginanneschi M Pinto F Massacesi L Papini AM 《Bioorganic & medicinal chemistry letters》1999,9(2):167-172
Glycopeptides of hMOG(30-50) containing a glucosyl moiety on the side-chains of Asn, Ser or Hyp at position 31 were synthesised. Antibody titres to hMOG(30-50) and to its glucoderivatives were measured by ELISA in sera of patients affected by different neurological diseases. Anti-hMOG(30-50) antibodies were detected only using the glycopeptide [Asn31(N-Glc)]hMOG(30-50). 相似文献
927.
Florencia Eberhardt Andres Aguirre Hugo G. Menzella Salvador Peiru 《Journal of industrial microbiology & biotechnology》2017,44(1):141-147
Biodiesels produced from transesterification of vegetable oils have a major problem in quality due to the presence of precipitates, which are mostly composed of steryl glucosides (SGs). We have recently described an enzymatic method for the efficient removal of SGs from biodiesel, based on the activity of a thermostable β-glycosidase from Thermococcus litoralis. In the present work, we describe the development of an Escherichia coli-based expression system and a high cell density fermentation process. Strain and process engineering include the assessment of different promoters to drive the expression of a codon-optimized gene, the co-expression of molecular chaperones and the development of a high cell density fermentation process. A 200-fold increase in the production titers was achieved, which directly impacts on the costs of the industrial process for treating biodiesel. 相似文献
928.
Restoring the flooding‐related disturbance regime by removing and setting back flood defenses (channel widening) is the most efficient strategy for recovering riparian plant communities in floodplains formerly impacted by human activities such as agriculture, mining, and forestry. Removing flood defenses is generally not socially accepted, and alternative recovery strategies must be explored. We assessed vegetation establishment on 33 sites in the floodplains of the Middle Ebro River and three of its tributaries (NE Spain) where restoration approaches applied in the last 20 years include channel widening, floodplain excavation, and abandonment of agriculture, gravel extraction, and hybrid poplar plantations, with and without plantation of native species. Using analysis of similarity and ordinations, we found that channel widening led to plant communities closely resembling those found on natural gravel bars, including new recruits of keystone tree species. Excavation of the floodplain as the restoration approach resulted in pioneer, non‐strictly riparian communities. Abandonment of agricultural land or clearing of poplar plantations resulted in alternative stable states predominating, regardless of time elapsed since restoration and whether poles of native species were planted. However, forest‐like communities relatively similar to mature, natural riparian references were attainable when hybrid poplars were allowed to resprout after clear‐cutting, or after the human activities were abandoned and trees were not cut. Combining channel widening and assisted revegetation where flood defenses cannot be altered may partially reproduce a mosaic of habitats typical of natural floodplains. 相似文献
929.
Jiří Šmíd Mohammed Shobrak Thomas Wilms Ulrich Joger Salvador Carranza 《Organisms Diversity & Evolution》2017,17(1):267-285
In this study, we provide genetic, morphological, and geographical comparisons for 11 species of the southwestern Arabian radiation of Hemidactylus geckos, nine of which are endemic to the region. By using a coalescence-based species-tree reconstruction in combination with divergence time estimations and speciation probability testing, we show that most of the speciation events occurred in the Pliocene, which is more recent than previously thought based on calibrations of concatenated data sets. The current dating indicates that the changing climate at the beginning of the Pliocene, from hot and dry to cold and wet, is likely responsible for increased speciation in Hemidactylus. Analyses of geographic and altitudinal overlap of the species and their morphological differentiation show that most species do not occur in sympatry. Those that overlap geographically are usually differentiated by their altitudinal preference, head shape, body size, or their combination. Our results indicate that the topographically complex mountains of southwestern Arabia support a significant radiation of Hemidactylus geckos by allowing multiple allopatric speciation events to occur in a relatively small area. Consequently, we describe two new species endemic to the Asir Mountains of Saudi Arabia, H. alfarraji sp. n. and H. asirensis sp. n., and elevate two former subspecies of H. yerburii to a species level, H. montanus and H. pauciporosus. 相似文献
930.