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71.
Zinkernagel RM 《Cellular and molecular life sciences : CMLS》2012,69(10):1635-1640
So-called ‘immunological memory’ is, in my view, a typical example where a field of enquiry, i.e. to understand long-term
protection to survive reexposure to infection, has been overtaken by ‘l’art pour l’art’ of ‘basic immunology’. The aim of
this critical review is to point out some key differences between academic text book-defined immunological memory and protective
immunity as viewed from a co-evolutionary point of view, both from the host and the infectious agents. A key conclusion is
that ‘immunological memory’ of course exists, but only in particular experimental laboratory models measuring ‘quicker and
better’ responses after an earlier immunization. These often do correlate with, but are not the key mechanisms of, protection.
Protection depends on pre-existing neutralizing antibodies or pre-activated T cells at the time of infection—as documented
by the importance of maternal antibodies around birth for survival of the offspring. Importantly, both high levels of antibodies
and of activated T cells are antigen driven. This conclusion has serious implications for our thinking about vaccines and
maintaining a level of protection in the population to deal with old and new infectious diseases. 相似文献
72.
Tamara Jefferson Ulrich auf dem Keller Caroline Bellac Verena V. Metz Claudia Broder Jana Hedrich Anke Ohler Wladislaw Maier Viktor Magdolen Erwin Sterchi Judith S. Bond Arumugam Jayakumar Heiko Traupe Athena Chalaris Stefan Rose-John Claus U. Pietrzik Rolf Postina Christopher M. Overall Christoph Becker-Pauly 《Cellular and molecular life sciences : CMLS》2013,70(2):309-333
The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and β we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)—the constitutive α-secretase—is activated by meprin β through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin β, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin?/? mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes. 相似文献
73.
Translational activation of the lck proto-oncogene 总被引:44,自引:0,他引:44
74.
H. Meier 《Cellular and molecular life sciences : CMLS》1969,25(9):965-968
Zusammenfassung Der Aussendiameter der Muskelspindeln variert in Mäusen von Muskel zu Muskel. Der Grössenunterschied ist altersunabhängig. In Mäusen mit vererblichen neuromuskulären Erkrankungen wurden nur geringe Abnormitäten der Spindeln gefunden. Anscheinend sind sie erkrankungsresistent oder entwickeln sich erst im späteren Erkrankungsprozess. 相似文献
75.
Ritter C Maddelein ML Siemer AB Lührs T Ernst M Meier BH Saupe SJ Riek R 《Nature》2005,435(7043):844-848
Prions are believed to be infectious, self-propagating polymers of otherwise soluble, host-encoded proteins. This concept is now strongly supported by the recent findings that amyloid fibrils of recombinant prion proteins from yeast, Podospora anserina and mammals can induce prion phenotypes in the corresponding hosts. However, the structural basis of prion infectivity remains largely elusive because acquisition of atomic resolution structural properties of amyloid fibrils represents a largely unsolved technical challenge. HET-s, the prion protein of P. anserina, contains a carboxy-terminal prion domain comprising residues 218-289. Amyloid fibrils of HET-s(218-289) are necessary and sufficient for the induction and propagation of prion infectivity. Here, we have used fluorescence studies, quenched hydrogen exchange NMR and solid-state NMR to determine the sequence-specific positions of amyloid fibril secondary structure elements of HET-s(218-289). This approach revealed four beta-strands constituted by two pseudo-repeat sequences, each forming a beta-strand-turn-beta-strand motif. By using a structure-based mutagenesis approach, we show that this conformation is the functional and infectious entity of the HET-s prion. These results correlate distinct structural elements with prion infectivity. 相似文献
76.
An integrative genomics approach to infer causal associations between gene expression and disease 总被引:2,自引:0,他引:2
77.
Zusammenfassung Alle von uns in Mäusen untersuchten vererblichen neurologischen Erkrankungen stellen entweder primäre oder sekundäre gesamtkörperliche Prozesse dar. Verschiedene allelische Substitutionen produzieren spezifische Leber-Esterase-Isozym-Defekte.
This work was supported in part by NIH research grant No. NB 06448 from the National Institute of Neurological Diseases nad Stroke, a grant from the National Foundation for Neuromuscular Diseases, Inc., a grant from the Health Research Fund, United Fund of Schenectedy County, Inc., and an allocation from NIH General Research Support Grant No. RR 05545 from the Division of Research Resources to The Jackson Laboratory.
The principles of laboratory animal care as promulgated by the National Society for Medical Research are observed in this Laboratory. 相似文献
This work was supported in part by NIH research grant No. NB 06448 from the National Institute of Neurological Diseases nad Stroke, a grant from the National Foundation for Neuromuscular Diseases, Inc., a grant from the Health Research Fund, United Fund of Schenectedy County, Inc., and an allocation from NIH General Research Support Grant No. RR 05545 from the Division of Research Resources to The Jackson Laboratory.
The principles of laboratory animal care as promulgated by the National Society for Medical Research are observed in this Laboratory. 相似文献
78.
79.
Star B Nederbragt AJ Jentoft S Grimholt U Malmstrøm M Gregers TF Rounge TB Paulsen J Solbakken MH Sharma A Wetten OF Lanzén A Winer R Knight J Vogel JH Aken B Andersen O Lagesen K Tooming-Klunderud A Edvardsen RB Tina KG Espelund M Nepal C Previti C Karlsen BO Moum T Skage M Berg PR Gjøen T Kuhl H Thorsen J Malde K Reinhardt R Du L Johansen SD Searle S Lien S Nilsen F Jonassen I Omholt SW Stenseth NC Jakobsen KS 《Nature》2011,477(7363):207-210
Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC)?II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC?II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC?I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC?II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates. 相似文献
80.