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101.
102.
Phosphorylation-induced conformational switching of CPI-17 produces a potent myosin phosphatase inhibitor 总被引:1,自引:0,他引:1
Eto M Kitazawa T Matsuzawa F Aikawa S Kirkbride JA Isozumi N Nishimura Y Brautigan DL Ohki SY 《Structure (London, England : 1993)》2007,15(12):1591-1602
Phosphorylation of endogenous inhibitor proteins for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. A myosin phosphatase inhibitor protein CPI-17 is phosphorylated at Thr38 through G-protein-mediated signals, resulting in a >1000-fold increase in inhibitory potency. We show here the solution NMR structure of phospho-T38-CPI-17 with rmsd of 0.36 +/- 0.06 A for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes an inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side chains, which is not formed in a phospho-mimetic D38 form of CPI-17. Thus, the profound increase in potency of CPI-17 arises from phosphorylation, conformational change, and hydrophobic stabilization of a rigid structure that poses the phosphorylated residue on the protein surface and restricts its hydrolysis by myosin phosphatase. Our results provide structural insights into transduction of kinase signals by PP1 inhibitor proteins. 相似文献
103.
Thomas A. Kursar Catherina C. Caballero-George Todd L. Capson Luis Cubilla-Rios William H. Gerwick Maria V. Heller Alicia Ibañez Roger G. Linington Kerry L. McPhail Eduardo Ortega-Barría Luz I. Romero P. D. Coley 《Biodiversity and Conservation》2007,16(10):2789-2800
The limited international resources for economic aid and conservation can only mitigate poverty and losses of biodiversity.
Hence, developing nations must establish the capacity to resolve their problems. Additionally, policy-makers and donors need
to obtain scientific input on issues such as global change and ecosystem services. We propose that for nations rich in biodiversity,
ecosystem services derived from bioprospecting, or drug discovery, could contribute to economic development. In the case where
unstudied samples are shipped abroad for research, the chances of obtaining royalties are infinitesimally small. Therefore
developing nations will only realize benefits from bioprospecting through in-country research on their own biodiversity. Policy-makers
and donors have failed to appreciate the value of this approach. In order to provide an example of the inherent links between
conservation and sustainable economic development, we initiated a drug discovery effort in Panama that emphasizes local benefit.
As much of the drug discovery process as possible is conducted in Panamanian laboratories, providing jobs dependent on intact
biodiversity and enhancing local research and training. In short, research, plus the spin-offs from research, provide immediate
and long-lasting benefits to Panama. The connection between conservation and development has been highlighted in publicity
about the project in Panama’s urban media. This provides a constructive alternative to the perception the among the urban
populace that economic development inevitably competes with conservation. In summary, our program uses biodiversity to promote
human health as well as to support research capacity, economic development and conservation within Panama. The program provides
an example of the widely recognized but little developed concept of bioprospecting research as an ecosystem service. 相似文献
104.
Rodamilans B Ibañez S Bragado-Nilsson E Sarrias MR Lozano F Blanco FJ Montoya G 《Journal of structural biology》2007,159(1):144-148
The human lymphocyte receptor CD5, a key regulator of immune responses, is involved in the modulation of antigen specific receptor-mediated T cell activation and differentiation signals. CD5 is a membrane glycoprotein which belongs to the group B scavenger receptor cysteine-rich (SRCR) superfamily for which no structural information is available. The most conserved membrane-proximal SRCR domain of CD5 (domain III) has been expressed in HEK-EBNA-293 cells. Although the yield of the purified protein was at the level of micrograms, well diffracting crystals have been obtained. The crystals belong to a tetragonal space group P4(1)22 or P4(3)22. They contain two molecules per asymmetric unit and diffracted to 2.5A resolution using synchrotron radiation. The strategy shown here to produce, isolate and crystallize CD5 domain III can be used for other mammalian proteins difficult to produce for structural or other biophysical studies. 相似文献
105.
Yamada H Ohashi E Abe T Kusumi N Li SA Yoshida Y Watanabe M Tomizawa K Kashiwakura Y Kumon H Matsui H Takei K 《Molecular biology of the cell》2007,18(11):4669-4680
Amphiphysin 1 is involved in clathrin-mediated endocytosis. In this study, we demonstrate that amphiphysin 1 is essential for cellular phagocytosis and that it is critical for actin polymerization. Phagocytosis in Sertoli cells was induced by stimulating phosphatidylserine receptors. This stimulation led to the formation of actin-rich structures, including ruffles, phagocytic cups, and phagosomes, all of which showed an accumulation of amphiphysin 1. Knocking out amphiphysin 1 by RNA interference in the cells resulted in the reduction of ruffle formation, actin polymerization, and phagocytosis. Phagocytosis was also drastically decreased in amph 1 (-/-) Sertoli cells. In addition, phosphatidylinositol-4,5-bisphosphate-induced actin polymerization was decreased in the knockout testis cytosol. The addition of recombinant amphiphysin 1 to the cytosol restored the polymerization process. Ruffle formation in small interfering RNA-treated cells was recovered by the expression of constitutively active Rac1, suggesting that amphiphysin 1 functions upstream of the protein. These findings support that amphiphysin 1 is important in the regulation of actin dynamics and that it is required for phagocytosis. 相似文献
106.
Yamaguchi H Zhu J Yu T Sasaki K Umetsu H Kidachi Y Ryoyama K 《Cell biology international》2007,31(6):638-644
107.
Marcelo De Franco Patrícia dos Santos Carneiro Luciana Carla Peters Francisca Vorraro Andrea Borrego Orlando Garcia Ribeiro Nancy Starobinas Wafa Koury Cabrera Olga Martinez Ibañez 《Mammalian genome》2007,18(4):263-269
Lines of mice were obtained by selective breeding for maximum (AIRmax) or minimum (AIRmin) acute inflammation. They present
distinct neutrophil influx and show frequency disequilibrium of the solute carrier family 11a member 1
(Slc11a1) alleles. This gene is involved in ion transport at the endosomes within macrophages and neutrophils, interfering in their
activation. Homozygous AIRmax and AIRmin sublines for the Slc11a1 gene were produced to examine the interaction of this gene with the acute inflammatory loci. The present work investigated
wound-healing traits in AIRmax and AIRmin mice, in F1 and F2 intercrosses, and in Slc11a1 sublines. Two-millimeter ear punches were made in the mice and hole closure was measured during 40 days. AIRmax mice demonstrated
significant tissue repair while AIRmin mice did not. Significant differences between the responses of male and female mice
were also observed. Wound-healing traits demonstrated a correlation with neutrophil influx in F2 populations. AIRmax
SS
showed higher ear-wound closure than AIRmax
RR
mice, suggesting that the Slc11a1
S allele favored ear tissue repair. QTL analysis has detected two inflammatory loci modulating ear wound healing on chromosomes
1 and 14. These results suggest the involvement of the acute inflammation modifier QTL in the wound-healing phenotype. 相似文献
108.
Al-Mamun M Yamaki K Masumizu T Nakai Y Saito K Sano H Tamura Y 《International journal of biological sciences》2007,3(6):349-355
Free radicals are not only destructive to the living cells but also reduce the quality of animal products through oxidation. As a result the superoxide anion radical (O2-), one of the most destructive reactive oxygen species, is a matter of concern for the animal scientists as well as feed manufacturers to ensure the quality of product to reach consumers demand. The superoxide anion radical scavenging activities (SOSA) of water and MeOH extracts of 2 herbs and 9 pasture samples collected from lowland and highland swards were determined against a 5,5-dimethyl-1-pyroline-N-oxide-O2-spin adduct based on a hypoxanthine-xanthine oxidase reaction using electron spin resonance spectrometry. Both the water and MeOH extracted SOSA differed among the herbs and pastures. Species and altitudinal variations were observed between extraction methods. The herbs were higher in both water and MeOH extracted SOSA than the pastures except for water extracts of one pasture, white clover (Trifolium repens L.). Among the pastures, quackgrass (Agrophyron repens L.) showed higher SOSA in both the MeOH and water extracts, and timothy (Phleum pretense L.) showed higher MeOH extracted SOSA. It is apparent that the kind and amount of antioxidants differ among herbs and pastures. Animal health and quality of animal products could be improved by adequate selection and combining of herbs and pastures having higher SOSA. 相似文献
109.
Moriyama A Kii I Sunabori T Kurihara S Takayama I Shimazaki M Tanabe H Oginuma M Fukayama M Matsuzaki Y Saga Y Kudo A 《Genesis (New York, N.Y. : 2000)》2007,45(2):90-100
In the past decades, the function of the Wnt canonical pathway during embryogenesis has been intensively investigated; however, little survey of neonatal and adult tissues has been made, and the role of this pathway remains largely unknown. To investigate its role in mature tissues, we generated two new reporter transgenic mouse lines, ins-TOPEGFP and ins-TOPGAL, that drive EGFP and beta-galactosidase expression under TCF/beta-catenin, respectively. To obtain the accurate expression pattern, we flanked these transgenes with the HS4 insulator to reduce chromosomal positional effects. Analysis of embryos showed that the reporter genes were activated in regions where canonical Wnt activity has been implicated. Furthermore, their expression patterns were consistent in both lines, indicating the accuracy of the reporter signal. In the neonatal brain, the reporter signal was detected in the mesencephalon and hippocampus. In the adult mice, the reporter signal was found in the mature pericenteral hepatocytes in the normal liver. Furthermore, during inflammation the number of T cells expressing the reporter gene increased in the adult spleen. Thus, in this research, we identified two organs, i.e., the liver and spleen, as novel organs in which the Wnt canonical signal is in motion in the adult. These transgenic lines will provide us broader opportunities to investigate the function of the Wnt canonical pathway in vivo. 相似文献
110.
Hydrobiologia - During larval development of the intertidal barnacle Fistulobalanus albicostatus, larvae in the naupliar stages I and II (NI&II) possess a single naupliar eye, and later... 相似文献