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111.
112.
Microtubules of the mitotic spindle form the structural basis for chromosome segregation. In metaphase, microtubules show high dynamic instability, which is thought to aid the 'search and capture' of chromosomes for bipolar alignment on the spindle. Microtubules suddenly become more stable at the onset of anaphase, but how this change in microtubule behaviour is regulated and how important it is for the ensuing chromosome segregation are unknown. Here we show that in the budding yeast Saccharomyces cerevisiae, activation of the phosphatase Cdc14 at anaphase onset is both necessary and sufficient for silencing microtubule dynamics. Cdc14 is activated by separase, the protease that triggers sister chromatid separation, linking the onset of anaphase to microtubule stabilization. If sister chromatids separate in the absence of Cdc14 activity, microtubules maintain high dynamic instability; this correlates with defects in both the movement of chromosomes to the spindle poles (anaphase A) and the elongation of the anaphase spindle (anaphase B). Cdc14 promotes localization of microtubule-stabilizing proteins to the anaphase spindle, and dephosphorylation of the kinetochore component Ask1 contributes to both the silencing of microtubule turnover and successful anaphase A. 相似文献
113.
Apolipoprotein-mediated pathways of lipid antigen presentation 总被引:1,自引:0,他引:1
van den Elzen P Garg S León L Brigl M Leadbetter EA Gumperz JE Dascher CC Cheng TY Sacks FM Illarionov PA Besra GS Kent SC Moody DB Brenner MB 《Nature》2005,437(7060):906-910
Peptide antigens are presented to T cells by major histocompatibility complex (MHC) molecules, with endogenous peptides presented by MHC class I and exogenous peptides presented by MHC class II. In contrast to the MHC system, CD1 molecules bind lipid antigens that are presented at the antigen-presenting cell (APC) surface to lipid antigen-reactive T cells. Because CD1 molecules survey endocytic compartments, it is self-evident that they encounter antigens from extracellular sources. However, the mechanisms of exogenous lipid antigen delivery to CD1-antigen-loading compartments are not known. Serum apolipoproteins are mediators of extracellular lipid transport for metabolic needs. Here we define the pathways mediating markedly efficient exogenous lipid antigen delivery by apolipoproteins to achieve T-cell activation. Apolipoprotein E binds lipid antigens and delivers them by receptor-mediated uptake into endosomal compartments containing CD1 in APCs. Apolipoprotein E mediates the presentation of serum-borne lipid antigens and can be secreted by APCs as a mechanism to survey the local environment to capture antigens or to transfer microbial lipids from infected cells to bystander APCs. Thus, the immune system has co-opted a component of lipid metabolism to develop immunological responses to lipid antigens. 相似文献
114.
Zusammenfassung Es wird die Synthese von Diazoacetyl-cholin-bromid beschrieben. Die Verbindung zeigt in verschiedenen biologischen Präparaten starke acetyl-cholin-ähnliche Wirkung; sie wird von Acetylcholinesterase etwa 1.6×104 mal langsamer als Acetylcholiniodid hydrolysiert. Die Photolyse gelingt mit Wellenlängen grösser als 315 nm. Das hauptsächliche Photolyseprodukt in Wasser ist Hydroxyacetyl-cholin-bromid. Es scheint — entsprechend dem stark elektronegativen Charakter der Trimethylammoniumgruppe — dieWolff'sche Umlagerung nur in untergeordnetem Masse einzutreten. Aufgrund dieser Befunde soll die Eignung der Verbindung zur Affinitätsmarkierung von Acetylcholinesterase, Cholinacetyltransferase und von Rezeptormolekeln untersucht werden. 相似文献
115.
H. Baker O. Frank S. H. Hutner S. Aaronson H. Ziffer H. Sobotka 《Cellular and molecular life sciences : CMLS》1962,18(5):224-226
Résumé Les auteurs ont étudié le mécanisme de la toxicité de la primidone (Mysoline) chez certains microorganismes. Ces recherches montrent que le métabolisme de l'acide folique est inhibé par le primidone et cela en trois étapes: (a) la réduction de l'acide folique en acide dihydrofolique, (b) le métabolisme des ptéridines nonconjugées et (c) la phosphorylation de la thymidine.
This work was aided by grants from the National Vitamin Foundation, National Association for Mental Health, American Cancer Society, and U.S. Public Health Service. We thank Dr.Th. Robitcher, Ayerst Laboratories, New York, for aid and gifts of primidone and Dr.E. Patterson of the American Cyanamid Co., Pearl River, New York, for the gifts of unconjugated pteridine. 相似文献
This work was aided by grants from the National Vitamin Foundation, National Association for Mental Health, American Cancer Society, and U.S. Public Health Service. We thank Dr.Th. Robitcher, Ayerst Laboratories, New York, for aid and gifts of primidone and Dr.E. Patterson of the American Cyanamid Co., Pearl River, New York, for the gifts of unconjugated pteridine. 相似文献
116.
Hoogenraad CC Koekkoek B Akhmanova A Krugers H Dortland B Miedema M van Alphen A Kistler WM Jaegle M Koutsourakis M Van Camp N Verhoye M van der Linden A Kaverina I Grosveld F De Zeeuw CI Galjart N 《Nature genetics》2002,32(1):116-127
Williams syndrome is a neurodevelopmental disorder caused by the hemizygous deletion of 1.6 Mb on human chromosome 7q11.23. This region comprises the gene CYLN2, encoding CLIP-115, a microtubule-binding protein of 115 kD. Using a gene-targeting approach, we provide evidence that mice with haploinsufficiency for Cyln2 have features reminiscent of Williams syndrome, including mild growth deficiency, brain abnormalities, hippocampal dysfunction and particular deficits in motor coordination. Absence of CLIP-115 also leads to increased levels of CLIP-170 (a closely related cytoplasmic linker protein) and dynactin at the tips of growing microtubules. This protein redistribution may affect dynein motor regulation and, together with the loss of CLIP-115-specific functions, underlie neurological alterations in Williams syndrome. 相似文献
117.
Distal ureter morphogenesis depends on epithelial cell remodeling mediated by vitamin A and Ret 总被引:10,自引:0,他引:10
Batourina E Choi C Paragas N Bello N Hensle T Costantini FD Schuchardt A Bacallao RL Mendelsohn CL 《Nature genetics》2002,32(1):109-115
Almost 1% of human infants are born with urogenital abnormalities, many of which are linked to irregular connections between the distal ureters and the bladder. During development, ureters migrate by an unknown mechanism from their initial integration site in the Wolffian ducts up to the base of the bladder in a process that we call ureter maturation. Rara(-/-) Rarb2(-/-) mice display impaired vitamin A signaling and develop syndromic urogenital malformations similar to those that occur in humans, including renal hypoplasia, hydronephrosis and mega-ureter, abnormalities also seen in mice with mutations in the proto-oncogene Ret. Here we show that ureter maturation depends on formation of the 'trigonal wedge', a newly identified epithelial outgrowth from the base of the Wolffian ducts, and that the distal ureter abnormalities seen in Rara(-/-) Rarb2(-/-) and Ret(-/-) mutant mice are probably caused by a failure of this process. Our studies indicate that formation of the trigonal wedge may be essential for correct insertion of the distal ureters into the bladder, and that these events are mediated by the vitamin A and Ret signaling pathways. 相似文献
118.
Plasmodium, human and Anopheles genomics and malaria 总被引:6,自引:0,他引:6
The Plasmodium spp. parasites that cause malaria are transmitted to humans by Anopheles spp. mosquitoes. Scientists have now amassed a great body of knowledge about the parasite, its mosquito vector and human host. Yet this year there will be 300-500 million new malaria infections and 1-3 million deaths caused by the disease. We believe that integrated analyses of genome sequence, DNA polymorphisms, and messenger RNA and protein expression profiles will lead to greater understanding of the molecular basis of vector-human and host-parasite interactions and provide strategies to build upon these insights to develop interventions to mitigate human morbidity and mortality from malaria. 相似文献
119.
van Kolfschooten F 《Nature》2002,416(6879):360-363
120.
A candidate prostate cancer susceptibility gene at chromosome 17p 总被引:23,自引:0,他引:23
Tavtigian SV Simard J Teng DH Abtin V Baumgard M Beck A Camp NJ Carillo AR Chen Y Dayananth P Desrochers M Dumont M Farnham JM Frank D Frye C Ghaffari S Gupte JS Hu R Iliev D Janecki T Kort EN Laity KE Leavitt A Leblanc G McArthur-Morrison J Pederson A Penn B Peterson KT Reid JE Richards S Schroeder M Smith R Snyder SC Swedlund B Swensen J Thomas A Tranchant M Woodland AM Labrie F Skolnick MH Neuhausen S Rommens J Cannon-Albright LA 《Nature genetics》2001,27(2):172-180
It is difficult to identify genes that predispose to prostate cancer due to late age at diagnosis, presence of phenocopies within high-risk pedigrees and genetic complexity. A genome-wide scan of large, high-risk pedigrees from Utah has provided evidence for linkage to a locus on chromosome 17p. We carried out positional cloning and mutation screening within the refined interval, identifying a gene, ELAC2, harboring mutations (including a frameshift and a nonconservative missense change) that segregate with prostate cancer in two pedigrees. In addition, two common missense variants in the gene are associated with the occurrence of prostate cancer. ELAC2 is a member of an uncharacterized gene family predicted to encode a metal-dependent hydrolase domain that is conserved among eukaryotes, archaebacteria and eubacteria. The gene product bears amino acid sequence similarity to two better understood protein families, namely the PSO2 (SNM1) DNA interstrand crosslink repair proteins and the 73-kD subunit of mRNA 3' end cleavage and polyadenylation specificity factor (CPSF73). 相似文献