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701.
Dumoulin M Last AM Desmyter A Decanniere K Canet D Larsson G Spencer A Archer DB Sasse J Muyldermans S Wyns L Redfield C Matagne A Robinson CV Dobson CM 《Nature》2003,424(6950):783-788
Amyloid diseases are characterized by an aberrant assembly of a specific protein or protein fragment into fibrils and plaques that are deposited in various organs and tissues, often with serious pathological consequences. Non-neuropathic systemic amyloidosis is associated with single point mutations in the gene coding for human lysozyme. Here we report that a single-domain fragment of a camelid antibody raised against wild-type human lysozyme inhibits the in vitro aggregation of its amyloidogenic variant, D67H. Our structural studies reveal that the epitope includes neither the site of mutation nor most residues in the region of the protein structure that is destabilized by the mutation. Instead, the binding of the antibody fragment achieves its effect by restoring the structural cooperativity characteristic of the wild-type protein. This appears to occur at least in part through the transmission of long-range conformational effects to the interface between the two structural domains of the protein. Thus, reducing the ability of an amyloidogenic protein to form partly unfolded species can be an effective method of preventing its aggregation, suggesting approaches to the rational design of therapeutic agents directed against protein deposition diseases. 相似文献
702.
703.
M. V. Nogués M. Moussaoui E. Boix M. Vilanova M. Ribó C. M. Cuchillo 《Cellular and molecular life sciences : CMLS》1998,54(8):766-774
The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment
between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases,
enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and
basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in
the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized
by structural and kinetic studies. In addition to the active site (p1 ), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been
proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3′ side and 5′ side, respectively,
of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2 , and Lys-66 in p0 ) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A.
The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA. 相似文献
704.
Components of biological,including seasonal,variation in hematological measurements and plasma fibrinogen concentrations in normal humans 总被引:2,自引:0,他引:2
M. Maes S. Scharpé W. Cooreman A. Wauters H. Neels R. Verkerd F. De Meyer P. D'Hondt D. Peeters P. Cosyns 《Cellular and molecular life sciences : CMLS》1995,51(2):141-149
This study has been carried out in order to examine the components of biologicalaand, in particular, seasonal variation in hematologic measurements in normal humans. Toward this end, 26 normal volunteers had monthly blood samplings during one calendar year for determination of number of red blood cells (RBC) and platelets, hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), MC Hb (MCH), MC Hb concentration (MCHC), RBC distribution width (RDW), mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), and plasma fibrinogen concentrations. The data were analyzed by means of spectral analyses of a group of time series or a single time series, and by means of repeated measures analyses of variance. Most of the hematologic variables show seasonal rhythms, such as annual rhythms or harmonics, which are expressed as a group phenomenon. An important part of the variance (>15%) in Ht, MCV, MCH, MCHC, RDW, number of platelets, MPV and plasma fibrinogen was explained by a yearly variation. The peak-trough differences (expressed as a percentage of the mean) in the yearly variations in number of RBC, Ht, MCV, MCH, MCHC and RDW were very low (all<8.5%). Number of platelets (14.4%) and plasma fibrinogen values (28%) showed a high-amplitude yearly variation. All hematological variables, except MCHC, show a high interindividual variability which exceeds by far the intraindividual variability. 相似文献
705.
Hepatitis B virus (HBV) DNA frequently integrates into the genome of human primary liver cancer cells, but the significance of this integration in liver carcinogenesis is still unclear. Here we report the cloning of a single HBV integration site in a human hepatocellular carcinoma at an early stage of development, and of its germline counterpart. The normal locus was found to be transcribed into two polyadenylated messenger RNA species of 1.8 and 2.7 kilobases. We have isolated a complementary DNA clone from a normal adult human liver cDNA library which has an open reading frame with a coding capacity for a protein of 432 amino acids and relative molecular mass 48,536. The strong homology of the C-terminal half of the protein to the A-type cyclins of clam and Drosophila identifies it as a human cyclin A. The cyclin A gene has several exons, and the HBV integration occurs within an intron. As cyclins are important in the control of cell division, the disruption of a cyclin A gene by viral insertion might contribute to tumorigenesis. 相似文献
706.
T von Schantz G G?ransson G Andersson I Fr?berg M Grahn A Helgée H Wittzell 《Nature》1989,337(6203):166-169
Recent theory on sexual selection suggests that females in species without paternal care choose mates by their secondary sexual characters because these indicate genotypic quality which will be transmitted to the offspring. These ideas are not yet empirically supported as data quantifying the relationship between female mate choice and female reproductive success are lacking. Only in one case, in Colias butterflies, has it been demonstrated unequivocally that females choose 'good genotypes' as mates and there is only one study, on Drosophila, demonstrating that mate choice increases one component of offspring fitness. Spur length of male pheasants (Phasianus colchicus) correlates with various fitness-related properties. We here present the first experimental field data showing that female pheasants select mates on the basis of male spur length and that female mate choice correlates with female reproductive success. 相似文献
707.
D. Evéquoz E. Grouzmann A. G. Beck-Sickinger H. -R. Brunner B. Waeber 《Cellular and molecular life sciences : CMLS》1994,50(10):936-938
Neuropeptide Y (NPY) increases blood pressure either directly or indirectly by potentiating the effect of various vasoconstrictors. Only one (the Y1-receptor) of two subtypes of receptors (Y1 and Y2) is thought to mediate the vascular smooth muscle contraction. To test this hypothesis we challenged isolated rat mesenteric arteries that had a functional endothelium with (1–36) NPY and with specific Y1-receptor ([Leu31, Pro34] NPY) and Y2-receptor ([Ahx5–24, -Glu2--Lys30] NPY) agonists. The Y1-receptor agonist elicited a contractile response similar to that of NPY, whereas the Y2-receptor agonist had no effect on wall tension. We also found that the presence of a functional endothelium has no influence on the contractile response to NPY. From these data we conclude that the direct contractile effect of NPY in the mesenteric artery is mediated by stimulation of Y1-receptors and is not endothelium-dependent. 相似文献
708.
A single injection of cortisone or thyroxine to 8-day-old suckling mice initiates a temporary decrease of lactase activity. On the contrary, 3 injections of cortisone or thyroxine provoke a significant increase of lactase activity. It appears that the mechanism which controls the postnatal development of lactase in suckling animals is more complex than expected. 相似文献
709.
Summary Studies of the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configurations at C14 and C16 as well as the presence of the methoxycarbonyl group on C16 seem to play an essential role in the determination of biological activity.This work was supported by CNRS (A.T.P. No 3232).We thank Dr D. Pantaloni for interesting discussions, Drs N. and Y. Langlois for discussions and for supplying synthetic material, and Eli Lilly Laboratories for gifts of vinblastine, vincristine and leurosidine. 相似文献
710.
P P Grassé 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1977,284(2):141-142
Three British biologists have discovered that in the "bacteriophage phi X 174 genes D and E are translated from the same DNA sequence but in different reading frames." In 1973, the present author, on the basis of biological data and theoretical considerations, had foreseen existence of overlapping genes. The result of the British biologists confirms the hypothesis of P.-P. Grassé. 相似文献