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331.
Sayer JA Otto EA O'Toole JF Nurnberg G Kennedy MA Becker C Hennies HC Helou J Attanasio M Fausett BV Utsch B Khanna H Liu Y Drummond I Kawakami I Kusakabe T Tsuda M Ma L Lee H Larson RG Allen SJ Wilkinson CJ Nigg EA Shou C Lillo C Williams DS Hoppe B Kemper MJ Neuhaus T Parisi MA Glass IA Petry M Kispert A Gloy J Ganner A Walz G Zhu X Goldman D Nurnberg P Swaroop A Leroux MR Hildebrandt F 《Nature genetics》2006,38(6):674-681
332.
New protein folds have emerged throughout evolution, but it remains unclear how a protein fold can evolve while maintaining its function, particularly when fold changes require several sequential gene rearrangements. Here, we explored hypothetical evolutionary pathways linking different topological families of the DNA-methyltransferase superfamily. These pathways entail successive gene rearrangements through a series of intermediates, all of which should be sufficiently active to maintain the organism's fitness. By means of directed evolution, and starting from HaeIII methyltransferase (M.HaeIII), we selected all the required intermediates along these paths (a duplicated fused gene and duplicates partially truncated at their 5' or 3' coding regions) that maintained function in vivo. These intermediates led to new functional genes that resembled natural methyltransferases from three known classes or that belonged to a new class first seen in our evolution experiments and subsequently identified in natural genomes. Our findings show that new protein topologies can evolve gradually through multistep gene rearrangements and provide new insights regarding these processes. 相似文献
333.
Foser S Redwanz I Ebeling M Heizmann CW Certa U 《Cellular and molecular life sciences : CMLS》2006,63(19-20):2387-2396
A hallmark of resistance to type I interferons (IFNs) is the lack of antiproliferative responses. We show here that costimulation with IFN-alpha and transforming growth factor beta-1 (TGF-beta) potentiates antiproliferative activity in a sensitive (ME15) and resistant (D10) human melanoma cell line. A DNA microarray-based search for proliferation control genes involved that are cooperatively activated by IFN-alpha and TGF-beta, yielded 28 genes. Among these are the insulin-like growth factor-binding protein 3 (IGFBP3) and the calcium-binding protein S100A2; we demonstrate, that recombinant IGFBP3 protein is a potent growth inhibitor requiring TGF-beta activity. The antiproliferative activity of S100A2 is significantly enhanced by IFN-alpha in stably transfected ME15 or D10 cell lines. We show for the first time that IFN-alpha is a potent inducer of intracellular calcium release required for activation of S100A2. Our study provides a functional link between IFN-alpha and TGF-beta signaling and extends the function of IFN signaling to calcium-sensitive processes. 相似文献
334.
335.
Based on the classification of bacterial lipolytic enzymes, family I.3 lipase is a member of the large group of Gram-negative
bacterial true lipases. This lipase family is distinguished from other families not only by the amino acid sequence, but also
by the secretion mechanism. Lipases of family I.3 are secreted via the well-known type I secretion system. Like most of proteins
secreted via this system, family I.3 lipases are composed of two domains with distinct yet related functions. Recent years
have seen an increasing amount of research on this lipase family, in terms of isolation, secretion mechanism, as well as biochemical
and biophysical studies. This review describes our current knowledge on the structure-function relationships of family I.3
lipase, with an emphasis on its secretion mechanism.
Received 18 April 2006; received after revision 3 July 2006; accepted 24 August 2006 相似文献
336.
337.
Niimura N Arai S Kurihara K Chatake T Tanaka I Bau R 《Cellular and molecular life sciences : CMLS》2006,63(3):285-300
Neutron diffraction provides an experimental method of directly locating hydrogen atoms in proteins, a technique complimentary to ultra-high-resolution [1, 2] X-ray diffraction. Three different types of neutron diffractometers for biological macromolecules have been constructed in Japan, France and the United States, and they have been used to determine the crystal structures of proteins up to resolution limits of 1.5-2.5 A. Results relating to hydrogen positions and hydration patterns in proteins have been obtained from these studies. Examples include the geometrical details of hydrogen bonds, H/D exchange in proteins and oligonucleotides, the role of hydrogen atoms in enzymatic activity and thermostability, and the dynamical behavior of hydration structures, all of which have been extracted from these structural results and reviewed. Other techniques, such as the growth of large single crystals, the preparation of fully deuterated proteins, the use of cryogenic techniques, and a data base of hydrogen and hydration in proteins, will be described. 相似文献
338.
McTaggart SJ 《Cellular and molecular life sciences : CMLS》2006,63(3):255-267
Isoprenoids are synthesized in all living organisms and are incorporated into diverse classes of end-products that participate
in a multitude of cellular processes relating to cell growth, differentiation, cytoskeletal function and vesicle trafficking.
In humans, the non-sterol isoprenoids, farnesyl pyrophosphate and geranylgeranyl-pyrophosphate, are synthesized via the mevalonate
pathway and are covalently added to members of the small G protein superfamily. Isoprenylated proteins have key roles in membrane
attachment and protein functionality, have been shown to have a central role in some cancers and are likely also to be involved
in the pathogenesis and progression of atherosclerosis and Alzheimer disease. This review details current knowledge on the
biosynthesis of isoprenoids, their incorporation into proteins by the process known as prenylation and the complex regulatory
network that controls these proteins. An improved understanding of these processe is likely to lead to the development of
novel therapies that will have important implications for human health and disease.
Received 5 July 2005; received after revision 17 October 2005; accepted 22 October 2005 相似文献
339.
Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered
in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin
genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the
expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships
with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process,
the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong
oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely
licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign
antigens in some autoimmune and allergic diseases.
Received 25 October 2007; accepted 12 December 2007 相似文献
340.
Navarro S Aleu J Jiménez M Boix E Cuchillo CM Nogués MV 《Cellular and molecular life sciences : CMLS》2008,65(2):324-337
Human eosinophil cationic protein (ECP)/ ribonuclease 3 (RNase 3) is a protein secreted from the secondary granules of activated
eosinophils. Specific properties of ECP contribute to its cytotoxic activities associated with defense mechanisms. In this
work the ECP cytotoxic activity on eukaryotic cell lines is analyzed. The ECP effects begin with its binding and aggregation
to the cell surface, altering the cell membrane permeability and modifying the cell ionic equilibrium. No internalization
of the protein is observed. These signals induce cell-specific morphological and biochemical changes such as chromatin condensation,
reversion of membrane asymmetry, reactive oxygen species production and activation of caspase-3-like activity and, eventually,
cell death. However, the ribonuclease activity component of ECP is not involved in this process as no RNA degradation is observed.
In summary, the cytotoxic effect of ECP is attained through a mechanism different from that of other cytotoxic RNases and
may be related with the ECP accumulation associated with the inflammatory processes, in which eosinophils are present.
Received 26 October 2007; accepted 23 November 2007 相似文献