全文获取类型
收费全文 | 59526篇 |
免费 | 5692篇 |
国内免费 | 24篇 |
出版年
2023年 | 210篇 |
2022年 | 456篇 |
2021年 | 1007篇 |
2020年 | 632篇 |
2019年 | 807篇 |
2018年 | 993篇 |
2017年 | 866篇 |
2016年 | 1477篇 |
2015年 | 2446篇 |
2014年 | 2714篇 |
2013年 | 3172篇 |
2012年 | 4222篇 |
2011年 | 4086篇 |
2010年 | 2600篇 |
2009年 | 2353篇 |
2008年 | 3391篇 |
2007年 | 3434篇 |
2006年 | 3260篇 |
2005年 | 3094篇 |
2004年 | 3029篇 |
2003年 | 2772篇 |
2002年 | 2704篇 |
2001年 | 872篇 |
2000年 | 713篇 |
1999年 | 815篇 |
1998年 | 854篇 |
1997年 | 590篇 |
1996年 | 513篇 |
1995年 | 470篇 |
1994年 | 499篇 |
1993年 | 494篇 |
1992年 | 626篇 |
1991年 | 500篇 |
1990年 | 488篇 |
1989年 | 494篇 |
1988年 | 441篇 |
1987年 | 414篇 |
1986年 | 403篇 |
1985年 | 379篇 |
1984年 | 434篇 |
1983年 | 399篇 |
1982年 | 421篇 |
1981年 | 383篇 |
1980年 | 396篇 |
1979年 | 311篇 |
1978年 | 300篇 |
1977年 | 264篇 |
1976年 | 257篇 |
1974年 | 233篇 |
1973年 | 208篇 |
排序方式: 共有10000条查询结果,搜索用时 156 毫秒
991.
992.
993.
Stereoselectivity of the Chinese hamster ovary cell sialidase: sialoside hydrolysis with overall retention of configuration 总被引:1,自引:1,他引:0
The stereochemical course of enzymatic hydrolysis by the solublesialidase from Chinese hamster ovary cells, expressed as a recombinantprotein in insect Sf9 cells, was determined using proton nuclearmagnetic resonance spectroscopy. 4-Methyl umbelliferyl-N-acetylneuraminic acid was employed as substrate, and the stereoselectivityof the enzyme catalysis was ascertained by monitoring the H3axial and equatorial protons of the sialic acid product overthe reaction course. At both high (3 U) and low concentrations(1 U) of the enzyme, the alpha anomer of the sialic acid wasclearly observed as the initial reaction product. The correspondingbeta anomer of sialic acid appeared much later in the reaction,arising from mutarotation of the alpha anomer. Similar studieswere also carried out using the Salmonella typhimurium LT 2sialidase, a protein of similar size and substrate specificity.Both enzymes apparently cleave the alpha linked sialoside substratewith retention of configuration. Based on the observations ofa wide variety of other glycohydrolytic enzymes that have showna strong correlation of the stereoselectivity of catalysis withactive site topology (Gebler et al, J. Biol. Chem. 267, 1255912561,1992), the results obtained here suggest that the microbialand mammalian sialidases have a homologous active site architectureeven though the molecules do not share significant primary sequencesimilarities. sialidase NMR enzyme mechanism Chinese hamster 相似文献
994.
995.
M. R. Evans A. L. R. Thomas 《Proceedings. Biological sciences / The Royal Society》1997,264(1379):211-217
Studies of the evolution of elaborate ornaments have concentrated on their role in increasing attractiveness to mates. The classic examples of such sexually selected structures are the elongated tails of some bird species. Elongated tails can be divided into three categories: graduated tails, pin tails and streamers. There seems to be little debate about whether graduated and pin tails are ornaments; i.e. costly signals used in mate choice. However, in the case of streamers there is considerable discussion about their function. It has been suggested that tail streamers could be (i) entirely naturally selected, (ii) entirely sexually selected, (iii) partly naturally and partly sexually selected. The prime example of a species with tail streamers is the swallow (Hirundo rustica) in which both sexes have tail streamers. In this paper we discuss the aerodynamic consequences of different types of manipulation of the streamer and/or outer tail feather. We make qualitative predictions about the aerodynamic performance of swallows with manipulated tail streamers; these predictions differ depending on whether streamers have a naturally or sexually selected function. We demonstrate that these hypotheses can only be separated if tail streamers are shortened and changes in aerodynamic performance measured during turning flight. 相似文献
996.
N. Yamazaki R. Ueshima J. A. Terrett S. I. Yokobori M. Kaifu R. Segawa T. Kobayashi K. I. Numachi T. Ueda K. Nishikawa K. Watanabe R. H. Thomas 《Genetics》1997,145(3):749-758
Complete gene organizations of the mitochondrial genomes of three pulmonate gastropods, Euhadra herklotsi, Cepaea nemoralis and Albinaria coerulea, permit comparisons of their gene organizations. Euhadra and Cepaea are classified in the same superfamily, Helicoidea, yet they show several differences in the order of tRNA and protein coding genes. Albinaria is distantly related to the other two genera but shares the same gene order in one part of its mitochondrial genome with Euhadra and in another part with Cepaea. Despite their small size (14.1-14.5 kbp), these snail mtDNAs encode 13 protein genes, two rRNA genes and at least 22 tRNA genes. These genomes exhibit several unusual or unique features compared to other published metazoan mitochondrial genomes, including those of other molluscs. Several tRNAs predicted from the DNA sequences possess bizarre structures lacking either the T stem or the D stem, similar to the situation seen in nematode mt-tRNAs. The acceptor stems of many tRNAs show a considerable number of mismatched basepairs, indicating that the RNA editing process recently demonstrated in Euhadra is widespread in the pulmonate gastropods. Strong selection acting on mitochondrial genomes of these animals would have resulted in frequent occurrence of the mismatched basepairs in regions of overlapping genes. 相似文献
997.
The mangroves of Kerala on the south-west coast of India are fast disappearing due to land reclamation and other anthropogenic
disturbances. There are very few ecosystem level studies made in these much threatened biotopes in Kerala. The present study
involves the measurement of heavy metals in the mangrove flora and sediments of three mangrove habitats along the Kerala coast.
Sampling was carried out for a period of one year at bi-monthly intervals, with concentrations of Fe, Mn, Cu,Zn,Pb and Co
analysed using atomic absorption spectrophotometry. An appreciable variation was observed in metal concentrations indifferent
mangrove species. Cu, Zn and Pb were found to be in higher concentrations in Avicennia officinalis whereas higher levels of
Fe, Mn and Co were observed in the species Barringtonia racemosa. The analysis of heavy metals indicated a high level of metal
pollutants such as Fe, Cu, Zn and Pb in the mangrove habitats of Quilon and Veli compared to the relatively uncontaminated
areas of Kumarakom.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
998.
I.J. East H. Zakrzewski K.R. Gale G. Leatch C.M. Dimmock M.B. Thomas D.J. Waltisbuhl 《International journal for parasitology》1997,27(12):1537-1545
Vaccination of cattle against the haemoprotozoun parasite, Babesia bovis, with the recombinant antigen 11C5 resulted in 9 of 15 cattle being protected against challenge infection. The cellular immune responses of protected and unprotected cattle were compared in order to identify differences in response. No differences were observed in the pattern of change in various blood leukocyte populations throughout challenge infection. FACScan analysis revealed an increase in the proportion of cells bearing the CD2 marker in both protected and unprotected cattle over the course of infection. There were no observable differences in the frequency of various cell-surface markers between the unprotected and protected cattle. During the period of patent parasitaemia, in vitro cultures of peripheral blood mononuclear cells (PBMC) from protected cattle produced significantly more TNF- (P < 0.05) than cultures from unprotected cattle. TNF- concentrations remained at pre-challenge levels until day 10, when levels in the unvaccinated control and vaccinated/unprotected animals dropped. By peak parasitaemia, TNF- production in vitro was siguificantly greater (P < 0.05) in cultures of PBMCs from protected cattle. Interferon production showed an initial peak at day 5 in all cattle, followed by a decrease and a second peak at days 10–13 in protected cattle only, which coincided with resolution of the infection. 相似文献
999.
Temperate Myxococcus xanthus phage Mx8 encodes a DNA adenine methylase, Mox. 总被引:1,自引:0,他引:1 下载免费PDF全文
V Magrini D Salmi D Thomas S K Herbert P L Hartzell P Youderian 《Journal of bacteriology》1997,179(13):4254-4263
Temperate bacteriophage Mx8 of Myxococcus xanthus encapsidates terminally repetitious DNA, packaged as circular permutations of its 49-kbp genome. During both lytic and lysogenic development, Mx8 expresses a nonessential DNA methylase, Mox, which modifies adenine residues in occurrences of XhoI and PstI recognition sites, CTCGAG and CTGCAG, respectively, on both phage DNA and the host chromosome. The mox gene is necessary for methylase activity in vivo, because an amber mutation in the mox gene abolishes activity. The mox gene is the only phage gene required for methylase activity in vivo, because ectopic expression of mox as part of the M. xanthus mglBA operon results in partial methylation of the host chromosome. The predicted amino acid sequence of Mox is related most closely to that of the methylase involved in the cell cycle control of Caulobacter crescentus. We speculate that Mox acts to protect Mx8 phage DNA against restriction upon infection of a subset of natural M. xanthus hosts. One natural isolate of M. xanthus, the lysogenic source of related phage Mx81, produces a restriction endonuclease with the cleavage specificity of endonuclease BstBI. 相似文献
1000.
Inbok Paek Lelio Orci Mariella Ravazzola Hediye Erdjument-Bromage Mylene Amherdt Paul Tempst Thomas H. S?llner James E. Rothman 《The Journal of cell biology》1997,137(5):1017-1028
We report the identification and characterization of ERS-24 (Endoplasmic Reticulum SNARE of 24 kD), a new mammalian v-SNARE implicated in vesicular transport between the ER and the Golgi. ERS24 is incorporated into 20S docking and fusion particles and disassembles from this complex in an ATP-dependent manner. ERS-24 has significant sequence homology to Sec22p, a v-SNARE in Saccharomyces cerevisiae required for transport between the ER and the Golgi. ERS-24 is localized to the ER and to the Golgi, and it is enriched in transport vesicles associated with these organelles.Newly formed transport vesicles have to be selectively targeted to their correct destinations, implying the existence of a set of compartment-specific proteins acting as unique receptor–ligand pairs. Such proteins have now been identified (Söllner et al., 1993a
; Rothman, 1994): one partner efficiently packaged into vesicles, termed a v-SNARE,1 and the other mainly localized to the target compartment, a t-SNARE. Cognate pairs of v- and t-SNAREs, capable of binding each other specifically, have been identified for the ER–Golgi transport step (Lian and Ferro-Novick, 1993; Søgaard et al., 1994), the Golgi–plasma membrane transport step (Aalto et al., 1993; Protopopov et al., 1993; Brennwald et al., 1994) in Saccharomyces cerevisiae, and regulated exocytosis in neuronal synapses (Söllner et al., 1993a
; for reviews see Scheller, 1995; Südhof, 1995). Additional components, like p115, rab proteins, and sec1 proteins, appear to regulate vesicle docking by controlling the assembly of SNARE complexes (Søgaard et al., 1994; Lian et al., 1994; Sapperstein et al., 1996; Hata et al., 1993; Pevsner et al., 1994).In contrast with vesicle docking, which requires compartment-specific components, the fusion of the two lipid bilayers uses a more general machinery derived, at least in part, from the cytosol (Rothman, 1994), which includes an ATPase, the N-ethylmaleimide–sensitive fusion protein (NSF) (Block et al., 1988; Malhotra et al., 1988), and soluble NSF attachment proteins (SNAPs) (Clary et al., 1990; Clary and Rothman, 1990; Whiteheart et al., 1993). Only the assembled v–t-SNARE complex provides high affinity sites for the consecutive binding of three SNAPs (Söllner et al., 1993b
; Hayashi et al., 1995) and NSF. When NSF is inactivated in vivo, v–t-SNARE complexes accumulate, confirming that NSF is needed for fusion after stable docking (Søgaard et al., 1994).The complex of SNAREs, SNAPs, and NSF can be isolated from detergent extracts of cellular membranes in the presence of ATPγS, or in the presence of ATP but in the absence of Mg2+, and sediments at ∼20 Svedberg (20S particle) (Wilson et al., 1992). In the presence of MgATP, the ATPase of NSF disassembles the v–t-SNARE complex and also releases SNAPs. It seems likely that this step somehow initiates fusion.To better understand vesicle flow patterns within cells, it is clearly of interest to identify new SNARE proteins. Presently, the most complete inventory is in yeast, but immunolocalization is difficult in yeast compared with animal cells, and many steps in protein transport have been reconstituted in animal extracts (Rothman, 1992) that have not yet been developed in yeast. Therefore, it is important to create an inventory of SNARE proteins in animal cells. The most unambiguous and direct method for isolating new SNAREs is to exploit their ability to assemble together with SNAPs and NSF into 20S particles and to disassemble into subunits when NSF hydrolyzes ATP. Similar approaches have already been successfully used to isolate new SNAREs implicated in ER to Golgi (Søgaard et al., 1994) and intra-Golgi transport (Nagahama et al., 1996), in addition to the original discovery of SNAREs in the context of neurotransmission (Söllner et al., 1993a
).Using this method, we now report the isolation and detailed characterization of ERS-24 (Endoplasmic Reticulum SNARE of 24 kD), a new mammalian v-SNARE that is localized to the ER and Golgi. ERS-24 is found in transport vesicles associated with the transitional areas of the ER and with the rims of Golgi cisternae, suggesting a role for ERS-24 in vesicular transport between these two compartments. 相似文献