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881.
DNA mutations and aberrations are a problem for all forms of life. Eukaryotes specifically have developed ways of identifying and repairing various DNA mutations in a complex and refractory chromatin environment. The chromatin structure is much more than a packaging unit for DNA; it is dynamic. Cells utilize and manipulate chromatin for gene regulation, genome organization and maintenance of genome integrity. Once a DNA aberration has occurred, the various DNA repair machineries interact with chromatin proteins, such as the histone variant H2A.X, and chromatin remodeling machines of the SWI/SNF family to gain access and repair the lesion in a timely manner. Recent studies have thus begun to address the roles of chromatin proteins in DNA repair as well as to dissect the functions of DNA repair machinery in vitro on more physiological, nucleosomal templates. 相似文献
882.
Leizerman I Avunie-Masala R Elkabets M Fich A Gheber L 《Cellular and molecular life sciences : CMLS》2004,61(16):2060-2070
The kinesin-related protein HsEg5 plays essential roles in mitotic spindle dynamics. Although inhibition of HsEg5 has been suggested as an aid in cancer treatment, the effects of such inhibition on human cells have not been characterized. Here we studied the effects of monastrol, an allosteric HsEg5 inhibitor, on AGS and HT29 cell lines and compared them to those of taxol. While both cell lines were similarly sensitive to taxol, AGS cells were more sensitive to monastrol. The differences in sensitivity were determined by the degree of inhibitory effect on cell proliferation, reversibility of monastrol-induced G2/M arrest, intracellular phenotypes and induction of apoptosis. In both cell lines, monastrol-induced apoptosis was accompanied by mitochondrial membrane depolarization and poly-ADP-ribose polymerase 1 cleavage. In AGS, but not HT29 cells, monastrol-induced apoptosis involved a prominent cleavage of procaspases 8 and 3. While in AGS cells, monastrol induced the formation of symmetric microtubule asters only, in HT29 cells, asymmetric asters were also formed, which may be related to specific HsEg5 functions in HT29 cells.Received 18 February 2004; received after revision 30 May 2004; accepted 16 June 2004 相似文献
883.
Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines 总被引:2,自引:0,他引:2
Carralot JP Probst J Hoerr I Scheel B Teufel R Jung G Rammensee HG Pascolo S 《Cellular and molecular life sciences : CMLS》2004,61(18):2418-2424
In the context of developing a safe genetic vaccination strategy we tested and studied globin-stabilized mRNA-based
vaccination in mice. This vaccination strategy has the advantages of genetic vaccination (easy production, adaptability to
any disease and inexpensive storage when lyophilized), but not the drawbacks of DNA vaccination (long-term uncontrolled
expression of a transgene, possibility of integration into the host genome and possible induction of anti-DNA antibodies).
We report here that injection of naked -globin untranslated region (UTR)-stabilized mRNA coding for
-galactosidase is followed by detectable translation in vivo. In addition, we show that such a vaccination strategy
primes a T helper 2 (Th2) type of response which can be enhanced and shifted to a Th1-type immune response by application
of recombinant granulocyte/macrophage colony-stimulating factor 1 day after mRNA injection. Our data demonstrate that the
administration of globin UTR-stabilized mRNA is a versatile vaccination strategy that can be manipulated to fit the
requirement of antiviral, antibacterial or antitumor immunity.Received 14 June 2004; received after revision 19 July 2004; accepted 9 August 2004 相似文献
884.
Angiogenesis and signal transduction in endothelial cells 总被引:11,自引:0,他引:11
Muñoz-Chápuli R Quesada AR Angel Medina M 《Cellular and molecular life sciences : CMLS》2004,61(17):2224-2243
Endothelial cells receive multiple information from their environment that eventually leads them to progress along all the stages of the process of formation of new vessels. Angiogenic signals promote endothelial cell proliferation, increased resistance to apoptosis, changes in proteolytic balance, cytoskeletal reorganization, migration and, finally, differentiation and formation of a new vascular lumen. We aim to review herein the main signaling cascades that become activated in angiogenic endothelial cells as well as the opportunities of modulating angiogenesis through pharmacological interference with these signaling mechanisms. We will deal mainly with the mitogen-activated protein kinases pathway, which is very important in the transduction of proliferation signals; the phosphatidylinositol-3-kinase/protein kinase B signaling system, particularly essential for the survival of the angiogenic endothelium; the small GTPases involved in cytoskeletal reorganization and migration; and the kinases associated to focal adhesions which contribute to integrate the pathways from the two main sources of angiogenic signals, i.e. growth factors and the extracellular matrix.Received 13 February 2004; received after revision 25 March 2004; accepted 19 April 2004 相似文献
885.
886.
Overview of mammalian zinc transporters 总被引:27,自引:0,他引:27
887.
Loss-of-function mutations in LEMD3 result in osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis 总被引:11,自引:0,他引:11
Hellemans J Preobrazhenska O Willaert A Debeer P Verdonk PC Costa T Janssens K Menten B Van Roy N Vermeulen SJ Savarirayan R Van Hul W Vanhoenacker F Huylebroeck D De Paepe A Naeyaert JM Vandesompele J Speleman F Verschueren K Coucke PJ Mortier GR 《Nature genetics》2004,36(11):1213-1218
Osteopoikilosis, Buschke-Ollendorff syndrome (BOS) and melorheostosis are disorders characterized by increased bone density. The occurrence of one or more of these phenotypes in the same individual or family suggests that these entities might be allelic. We collected data from three families in which affected individuals had osteopoikilosis with or without manifestations of BOS or melorheostosis. A genome-wide linkage analysis in these families, followed by the identification of a microdeletion in an unrelated individual with these diseases, allowed us to map the gene that is mutated in osteopoikilosis. All the affected individuals that we investigated were heterozygous with respect to a loss-of-function mutation in LEMD3 (also called MAN1), which encodes an inner nuclear membrane protein. A somatic mutation in the second allele of LEMD3 could not be identified in fibroblasts from affected skin of an individual with BOS and an individual with melorheostosis. XMAN1, the Xenopus laevis ortholog, antagonizes BMP signaling during embryogenesis. In this study, LEMD3 interacted with BMP and activin-TGFbeta receptor-activated Smads and antagonized both signaling pathways in human cells. 相似文献
888.
Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome 总被引:11,自引:0,他引:11
Ferland RJ Eyaid W Collura RV Tully LD Hill RS Al-Nouri D Al-Rumayyan A Topcu M Gascon G Bodell A Shugart YY Ruvolo M Walsh CA 《Nature genetics》2004,36(9):1008-1013
Joubert syndrome is a congenital brain malformation of the cerebellar vermis and brainstem with abnormalities of axonal decussation (crossing in the brain) affecting the corticospinal tract and superior cerebellar peduncles. Individuals with Joubert syndrome have motor and behavioral abnormalities, including an inability to walk due to severe clumsiness and 'mirror' movements, and cognitive and behavioral disturbances. Here we identified a locus associated with Joubert syndrome, JBTS3, on chromosome 6q23.2-q23.3 and found three deleterious mutations in AHI1, the first gene to be associated with Joubert syndrome. AHI1 is most highly expressed in brain, particularly in neurons that give rise to the crossing axons of the corticospinal tract and superior cerebellar peduncles. Comparative genetic analysis of AHI1 indicates that it has undergone positive evolutionary selection along the human lineage. Therefore, changes in AHI1 may have been important in the evolution of human-specific motor behaviors. 相似文献
889.
Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus 总被引:22,自引:0,他引:22
Hong YK Foreman K Shin JW Hirakawa S Curry CL Sage DR Libermann T Dezube BJ Fingeroth JD Detmar M 《Nature genetics》2004,36(7):683-685
Kaposi sarcoma is considered a neoplasm of lymphatic endothelium infected with Kaposi sarcoma-associated herpesvirus. It is characterized by the expression of lymphatic lineage-specific genes by Kaposi sarcoma tumor cells. Here we show that infection of differentiated blood vascular endothelial cells with Kaposi sarcoma-associated herpesvirus leads to their lymphatic reprogramming; induction of approximately 70% of the main lymphatic lineage-specific genes, including PROX1, a master regulator of lymphatic development; and downregulation of blood vascular genes. 相似文献
890.