全文获取类型
收费全文 | 4215篇 |
免费 | 252篇 |
国内免费 | 3篇 |
出版年
2021年 | 39篇 |
2020年 | 45篇 |
2019年 | 36篇 |
2018年 | 47篇 |
2017年 | 44篇 |
2016年 | 66篇 |
2015年 | 126篇 |
2014年 | 152篇 |
2013年 | 214篇 |
2012年 | 267篇 |
2011年 | 241篇 |
2010年 | 180篇 |
2009年 | 179篇 |
2008年 | 199篇 |
2007年 | 248篇 |
2006年 | 255篇 |
2005年 | 262篇 |
2004年 | 225篇 |
2003年 | 196篇 |
2002年 | 227篇 |
2001年 | 53篇 |
2000年 | 40篇 |
1999年 | 72篇 |
1998年 | 82篇 |
1997年 | 38篇 |
1996年 | 46篇 |
1995年 | 47篇 |
1994年 | 56篇 |
1993年 | 35篇 |
1992年 | 40篇 |
1991年 | 36篇 |
1990年 | 46篇 |
1989年 | 20篇 |
1988年 | 32篇 |
1987年 | 25篇 |
1986年 | 26篇 |
1985年 | 34篇 |
1984年 | 42篇 |
1983年 | 29篇 |
1982年 | 35篇 |
1981年 | 31篇 |
1980年 | 33篇 |
1979年 | 17篇 |
1978年 | 28篇 |
1977年 | 20篇 |
1976年 | 23篇 |
1975年 | 20篇 |
1974年 | 25篇 |
1973年 | 27篇 |
1967年 | 15篇 |
排序方式: 共有4470条查询结果,搜索用时 15 毫秒
61.
62.
Lora Swenson Ruth Green Rolf Joerger Michael Haas Karen Scott Yunyi Wei Urszula Derewenda David M. Lawson Zygmunt S. Derewenda 《Proteins》1994,18(3):301-306
A neutral lipase from the filamentous fungus Rhizopus delemar has been crystallized in both its proenzyme and mature forms. Although the latter crystallizes readily and produces a variety of crystal forms, only one was found to be suitable for X-ray studies. It is monoclinic (C2, a = 92.8 Å, b = 128.9 Å, c = 78.3 Å, β = 135.8) with two molecules in the asymmetric unit related by a noncrystallographic diad. The prolipase crystals are orthorhombic (P212121, with a = 79.8 Å, b = 115.2 Å, c = 73.0 Å) and also contain a pair of molecules in the asymmetric unit. Initial results of molecular replacement calculations using the refined coordinates of the related lipase from Rhizomucor miehei identified the correct orientations and positions of the protein molecules in the unit cells of crystals of both proenzyme and the mature form. © 1994 John Wiley & Sons, Inc. 相似文献
63.
Aspergillus nidulans andPenicillium chrysogenum are related fungi that reproduce asexually by forming multicellular conidiophores and uninucleate conidia. InA. nidulans, spore maturation is controlled by thewetA (AwetA) regulatory gene. We cloned a homologous gene (PwetA) fromP. chrysogenum to determine if spore maturation is regulated by a similar mechanism in this species. ThePwetA andAwetA genes are similar in structure and functional organization. The inferred polypeptides share 77% overall amino acid sequence similarity, with several regions having > 85% similarity. The genes also had significant, local sequence similarities in their 5′ flanking regions, including conserved binding sites for the product of the regulatory geneabaA.PwetA fully complemented anA. nidulans wetA deletion mutation, demonstrating thatPwetA and its 5′ regulatory sequences function normally inA. nidulans. These results indicate that the mechanisms controlling sporulation inA. nidulans andP. chrysogenum are evolutionarily conserved. 相似文献
64.
Denis Vivien Emmanuelle Petitfrre Laurent Martiny Herv Sartelet Philippe Galra Bernard Haye Jean-Pierre Pujol 《Journal of cellular physiology》1993,155(3):437-444
The knowledge of transforming growth factor (TGF)-β receptors has greatly progressed in the recent years. TGF-β receptors type I and II have been implicated in the modulation of cell proliferation, whereas type III (betaglycan) may act as a component presenting TGF-β to its signaling receptors. In addition, four other proteins that bind TGF-β1 or TGF-β2 have been recently identified in some cell lines, three being anchored to the membrane through a glycosylphosphatidylinositol (GPI). Despite this knowledge, the molecular mechanism of signal transduction through the TGF-β receptors remain an enigma. TGF-β family does not signal via any of the classical pathways. As GPI anchors of membrane proteins have been implicated in the transduction of some hormonal effects, we investigated the putative role of GPI in signaling the TGF-β effects on the proliferation of rabbit articular chondrocytes (RAC). We previously showed that TGF-β1 increased DNA replication rate of RAC, with a recruitment of cells in G2/M followed by a subsequent mitosis wave. Here, we find that the factor causes specific GPI hydrolysis, with correlated increase of inositolphosphate glycan (IPG). This effect was specifically inhibited by antibodies that bind TGF-β1. Using [3H]-inositol labeling and Triton X-114 extraction, we demonstrate that a hydrophobic material from the membrane is cleaved by treatment of cell cultures with phosphatidylinositol specific phospholipase C (PI-PLC) or by exposure to TGF-β, supporting that a PI-anchored molecule gives rise to IPG by TGF-β-induced hydrolysis. The biological relevance of this hydrolysis was demonstrated by the enhancing effect of purified IPG on the DNA synthesis rate, which mimicked the TGF-β action. These results demonstrate that IPG could be an early messenger in the cellular signaling that mediates the effect of TGF-β on RAC growth. © 1993 Wiley-Liss, Inc. 相似文献
65.
Philip J. Rijken Rolf P. De Groot Nico Van Belzen Siegfried W. De Laat Johannes Boonstra Arie J. Verkleij 《Experimental cell research》1993,204(2)
Epidermal growth factor (EGF)-induced c-fos and c-jun expression is strongly suppressed in microgravity. We investigate here whether this is due to inhibition of processes occurring during the initiation of EGF-induced signal transduction. For this purpose, EGF-induced receptor clustering is used as a marker. The lateral distribution of EGF receptors is directly visualized at an ultrastructural level by the label-fracture method. Quantification of the receptor distributions shows that EGF-induced receptor redistribution is similar under normal and microgravity conditions. This suggests that microgravity influences EGF-induced signal transduction downstream of EGF binding and EGF receptor redistribution, but upstream of early gene expression in human A431 cells. 相似文献
66.
Because of its low solubility it is unlikely that elemental sulfur serves as the direct substrate for sulfur-reducing bacteria. To test the hypothesis that polysulfide may represent a soluble intermediate of sulfur reduction, the maximal polysulfide concentrations formed from elemental sulfur in aqueous sulfide solutions were measured at near neutral pH and at temperatures up to 90°C. The saturation concentrations decreased by two orders of magnitude when the pH was lowered from 7 to 6 at a given temperature, and increased about tenfold when the temperature was raised from 37°C to 90°C at a given pH. The dissolution of 0.1 mM zerovalent sulfur in 1 mM sulfide (H2S+HS–) required a pH of 7.5 at 20°C and of only 6.1 at 100°C. A comparison with the growth optima of sulfur-reducers suggests that polysulfide is present at sufficient concentration at the growth conditions of the Bacteria and the moderately acidophilic Archaea. Polysulfide is apparently not available at the growth conditions of the extremely acidophilic Archaea. Alternative mechanisms for the sulfur utilization under these conditions are discussed.Abbreviations MOPS
Morpholinopropanesulfonate
- PIPES
1,4 piperazine-N,N-bis(2-ethanesulfonate)
- HEPES
N-2-hydroxy-ethylpiperazine-N-ethanesulfonate 相似文献
67.
68.
69.
Tuo Li Annika J. E. Borg Leo Krammer Rolf Breinbauer Bernd Nidetzky 《Biotechnology and bioengineering》2023,120(6):1506-1520
Polyphenolic aglycones featuring two sugars individually attached via C-glycosidic linkage (di-C-glycosides) represent a rare class of plant natural products with unique physicochemical properties and biological activities. Natural scarcity of such di-C-glycosides limits their use-inspired exploration as pharmaceutical ingredients. Here, we show a biocatalytic process technology for reaction-intensified production of the di-C-β-glucosides of two representative phenol substrates, phloretin (a natural flavonoid) and phenyl-trihydroxyacetophenone (a phenolic synthon for synthesis), from sucrose. The synthesis proceeds via an iterative two-fold C-glycosylation of the respective aglycone, supplied as inclusion complex with 2-hydroxypropyl β-cyclodextrin for enhanced water solubility of up to 50 mmol/L, catalyzed by a kumquat di-C-glycosyltransferase (di-CGT), and it uses UDP-Glc provided in situ from sucrose by a soybean sucrose synthase, with catalytic amounts (≤3 mol%) of UDP added. Time course analysis reveals the second C-glycosylation as rate-limiting (0.4–0.5 mmol/L/min) for the di-C-glucoside production. With internal supply from sucrose keeping the UDP-Glc at a constant steady-state concentration (≥50% of the UDP added) during the reaction, the di-C-glycosylation is driven to completion (≥95% yield). Contrary to the mono-C-glucoside intermediate which is stable, the di-C-glucoside requires the addition of reducing agent (10 mmol/L 2-mercaptoethanol) to prevent its decomposition during the synthesis. Both di-C-glucosides are isolated from the reaction mixtures in excellent purity (≥95%), and their expected structures are confirmed by NMR. Collectively, this study demonstrates efficient glycosyltransferase cascade reaction for flexible use in natural product di-C-β-glucoside synthesis from expedient substrates. 相似文献
70.
Summary In Drosophila, mutations in a class of genes, the neurogenic genes, produce an excess of neurons. This neural hyperplasia has been attributed to the formation of more than the normal number of neuronal precursor cells at the expense of epidermal cells. In order to find out whether the neurogenic genes only act at this intial step of neurogenesis, we studied the replication pattern of the sensory organ precursor cells by monitoring BrdU incorporation in embryos mutant for Notch (N), Delta (Dl), mastermind (mam), almondex (amx), neuralized (neu), big brain (bib) and the Enhancer of split-Complex (E(spl)-C). Using temperature sensitive alleles of two of the neurogenic genes, DI and N, we also induced an acute increase of replicating sensory precursors by shifting briefly to the restricted temperature. We have found that the loss of function of all the seven neurogenic loci that were tested causes an increase in replicating sensory precursor cells, consistent with the model that these neurogenic genes normally participate in the process of restricting the number of neuronal precursors. Whereas the temporal pattern of replication appeared normal in mutants of five of the seven neurogenic loci, in N and mam embryos replicating PNS cells are present beyond the time when they normally undergo replication. Experiments with colchicine suggest that many of these late replicating cells may be newly emerging precursors and probably not additional cell divisions of already recruited precursors. Thus, different neurogenic genes may be required over different periods of time for the specification of sensory precursor cells.
Correspondence to: R. Bodmer 相似文献