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1.
We have established a series of 20 colorectal cancer cell lines and performed cytogenetic and RFLP analyses to show that the
recurrent genetic abnormalities of chromosomes 1, 5, 17 and 18 associated with multistep tumorigenesis in colorectal cancer,
and frequently detected as recurrent abnormalities in primary tumours, are also retained in long-term established cell lines.
Earlier studies by us and other investigators showed that allelic losses of chromosomes 1 and 17 in primary colorectal cancers
predicted poorer survival for the patients (P = 0.03). We utilized the cell lines to identify specific chromosomal sites or gene(s) on chromosomes 1 and 17 which confer
more aggressive phenotype. Cytogenetic deletions of chromosome 1p were detected in 14 out of the 20 (70%) cell lines, whereas
allelic deletions for 1p using polymorphic markers were detected in 13 out of 18 (72%) informative cell lines for at least
one polymorphic marker. We have performed Northern blotting, immunohistochemical staining (p53 mRNA, protein) and RFLP analysis
using several probes including p53 and nm23. RFLP analysis using a total of seven polymorphic markers located on 17p and 17q
arms showed allelic losses aroundthe p53 locus in 16 out of the 20 cell lines (80%), four of which were losses of thep53 locus itself. In addition, seven cell lines (out of nine informative cases) also showed losses of thenm23 gene, four with concurrent losses of thep53 locus, while the remaining three were homozygous. In addition, five out of seven cell lines withnm23 deletions were derived from hepatic metastatic tumours, and one cell line was obtained from recurrent tumour. A comparison
between allelic deletions of 1p and functional loss ofnm23 gene revealed a close association between these two events in cell lines derived from hepatic metastasis. Following immunohistochemical
staining, nine out of the twenty cell lines showed high levels (25–80%) of mutant p53, four showed intermediate levels (>20%),
and seven had undetectable levels of the protein. Of these seven, four showed complete absence of mRNA. Of the remaining three
cell lines one showed aberrant mRNA due to germline rearrangement of thep53 gene, whereas in two cell lines normal levels of mRNA were present. Nineteen of the 20 cell lines had normal germline configurations
for thep53 gene, while one showed a rearrangement. These data suggest that functional loss ofp53 andnm23 genes accomplished by a variety of mechanisms may be associated with poor prognosis and survival. In addition, concurrent
deletions of chromosome regions 17p, 17q and 1p were closely associated with high-stage hepatic metastatic disease. These
cell lines with well-characterized genetic alterations and known clinical history provide an invaluable source of material
for various biological and clinical studies relating to multistep colorectal tumorigenesis. 相似文献
2.
The enzymatic activity of salivary amylase bound to the surface of several species of oral streptococci was determined by the production of acid from starch and by the degradation of maltotetraose to glucose in a coupled, spectrophotometric assay. Most strains able to bind amylase exhibited functional enzyme on their surface and produced acid from the products of amylolytic degradation. These strains were unable to utilise starch in the absence of salivary amylase. Two strains failed to produce acid from starch, despite the presence of functional salivary amylase, because they could not utilise maltose. Strains that could not bind salivary amylase failed to produce acid from starch. In no case was all the bound salivary amylase active, and two strains of Streptococcus mitis which bound amylase did not exhibit any enzyme activity on their cell surface. The ability to bind amylase may confer a survival advantage on oral bacteria which inhabit hosts that consume diets containing starch. 相似文献
3.
CO dehydrogenase/acetyl-CoA synthase (CODH/ACS) is one of the four known nickel enzymes. It is a bifunctional protein that
catalyzes the oxidation of CO to CO2 at a nickel iron-sulfur cluster (Cluster C) and a remarkable condensation reaction between a methyl group (donated from a
methylated corrinoid iron-sulfur protein), carbon monoxide, and coenzyme A to form acetyl-CoA at a separate nickel iron-sulfur
cluster (Cluster A). This review focuses on the current understanding of the structure and function of Cluster A and on related
model chemistry. It describes studies that uncovered the first example of a biological organometallic reaction sequence. The
mechanism of acetyl-CoA synthesis includes enzymebound methylnickel, iron-carbonyl, and acylmetal intermediates. Discovery
of the methylnickel species constituted the first example of an alkylnickel species in biology and unveiled a new biological
role for nickel.
Received: 10 April 1996 / Accepted: 4 July 1996 相似文献
4.
D. C. Sigee 《Protoplasma》1982,110(2):112-120
Summary The uptake of63Ni into cells of the binucleate dinoflagellateGlenodinium foliaceum was investigated using insoluble compound light and electron microscope autoradiography. Cells labelled over a period of 2 hours showed active uptake throughout the whole population, with an increase in mean cell grain count when the labelling period was extended to 4 hours and 24 hours. The mean grain count did not vary with type of fixation (glutaraldehyde, paraformaldehyde or acetic alcohol) suggesting that retention of63 Ni is not a specific fixation-binding artefact. At light microscope level, silver grains were not localised to any major cell component, but with the greater resolution of electron microscope autoradiography, a high degree of localisation was demonstrated in the typical dinoflagellate (dinocaryotic) nucleus-which contained about 83% of the cell label (cytoplasm 16%, supernumerary nucleus 1%). Silver grain distribution within the dinocaryotic nucleus was consistent with some degree of localisation to the condensed chromatin.The autoradiographic results corroborate previous X-ray microanalytical data which demonstrated high levels of transition metals in dinoflagellate nuclei. The distinction between the two types of nucleus inGlenodinium is further emphasised, giving additional support to the concept of a separate phyllogenetic origin of the supernumerary nucleus. 相似文献
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7.
Two dodecachlorinated porphyrins, 2,3,7,8,12,13,17,18-octachloro-5,10,15,20-tetra(4-chlorophenyl)porphyrin free base (TCl12PPH2) and its nickel compound (TCl12PPNi), have been synthesized. Single-crystal X-ray diffraction analysis shows that porphyrin rings are heavily distorted and exhibit saddled conformations. The Soret and Q bands of two compounds are red-shifted compared to their non-chlorinated counterparts. Theoretical calculations reveal that the optical band gap of TCl12PPH2 is reduced, whereas that of TCl12PPNi remains almost the same as to its non-chlorinated nickel compound due to the concurrent lowering of HOMO and LUMO energy levels. The frontier molecular orbitals are degenerated due to the decrease of symmetry of the molecules. 相似文献
8.
The reaction of [Ni(pftp)] [pftp = N,N-propane-1,3-diyl-(6-formyl-4-methyliminatothiophenolato)] with hydroxylamine hydrochloride in the presence potassium acetate in MeOH resulted in the formation of the complex [Ni(LH2)] [L = N,N-propane-1,3-diyl-(4-methyl-2-methyliminato-6-methyloxime-thiophenolato)] in good yield. A single crystal X-ray diffraction structural determination showed a mononuclear nickel(II) complex with the new acyclic ligand LH2 that had been functionalised with two oxime groups containing an empty N(oxime)2S2 pocket to which another metal ion could be added. A further reaction of [Ni(LH2)] with NiCl2·6H2O, triethylamine and ammonium hexafluorophosphate in MeOH gave a dark red product that yielded red crystals of [Ni2(LH)]PF6·DMF via slow recrystallisation from a DMF/PriOH solvent mixture. A single crystal X-ray diffraction study of these crystals confirmed the presence of a dinuclear nickel(II) complex linked by a dithiolato-bridge. Both nickel(II) ions exhibited square-planar geometry where the metal centres are coordinated in two distinct cis-S2N(imine)2 and cis-S2N(oxime)2 binding sites provided by the new dicompartmental oxime/thiolate-containing ligand LH. 相似文献
9.
Douglas E. Caldwell James A. Brierley Córale L. Brierley 《Geomicrobiology journal》2013,30(4):375-377
This investigation documents the formation of Green Rust (GR) and immobilization of Ni 2+ in response to bacterial reduction of hydrous ferric oxide (HFO). In the absence of Ni 2+ , 79% of the total Fe(III) present as HFO was reduced; at 10 -3 and 10 -4 M Ni 2+ , 36% of the total Fe(III) was reduced, whereas 45 to 50% of the total Fe(III) was reduced at 10 -5 M Ni 2+ . The inhibitory effect of 10 -3 and 10 -4 M Ni 2+ on Fe(III)-reduction corresponded to a 50% decrease in number of viable cells relative to the Ni 2+ -free condition, and a 25% decrease at 10 -5 M Ni 2+ . A prominent GR peak at d = 10.9 nm was evident in X-ray diffraction patterns of postreduction residual solids from the cultures. Minor peaks arising for vivianite and magnetite were also present. In samples prepared for scanning electron microscopy, thin hexagonal plates of GR were easily distinguished as a solid phase transformation product of HFO. Small hexagonal sheets and fragments of larger GR plates were also observed in transmission electron microscopy whole mounts together with bacteria that were mineralized by surface precipitates of microcrystalline magnetite. Energy dispersive spectroscopy (EDS) confirmed that GR contained Fe and P, as well as Ni in those samples taken from the Ni 2+ -amended experiments. EDS detected neither P nor Ni in the magnetite precipitates associated with the bacterial cells. Dissolved Ni2 + concentrations decreased in an exponential fashion with respect to time in all experimental systems, corresponding to an overall first-order rate constant k of -0.030 day -1 . At the same time, a strong linear relationship (r 2 = 0.99) between the dissolved and solid phase Ni 2+ /Fe 2+ ratios over the entire period of the Fe(III)reduction experiments provided evidence that the solid-phase partitioning of Ni 2+ in GR extended from equilibrium solid-solution behavior. 相似文献
10.