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141.
Evolutionary Relationship of the Ligand-Gated Ion Channels and the Avermectin-Sensitive,Glutamate-Gated Chloride Channels 总被引:4,自引:0,他引:4
Demetrios K. Vassilatis Keith O. Elliston Philip S. Paress Michel Hamelin Joseph P. Arena James M. Schaeffer Lex H.T. Van der Ploeg Doris F. Cully 《Journal of molecular evolution》1997,44(5):501-508
Two cDNAs, GluClα and GluClβ, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin
class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707–711, 1994). Expression studies in Xenopus oocytes showed that GluClα and GluClβ have pharmacological profiles distinct from the glutamate-gated cation channels as
well as the γ-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of
related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined
the nucleotide sequence of the GluClα and GluClβ genes. In an attempt to understand the evolutionary relationship of these
channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic
analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several
intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position.
Phylogenetic analyses indicate that GluClα and GluClβ form a monophyletic subbranch in the ligand-gated ion channel superfamily
and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties
similar to GluClα and GluClβ, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride
channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination
with the distinct pharmacological properties demonstrate that GluClα and GluClβ belong to a discrete ligand-gated ion channel
family that may represent genes orthologous to the vertebrate glycine channels.
Received: 30 September 1996 / Accepted: 15 November 1996 相似文献
142.
Jerzy K. Kulski Silvana Gaudieri Matthew Bellgard Lois Balmer Keith Giles Hidetoshi Inoko Roger L. Dawkins 《Journal of molecular evolution》1997,45(6):599-609
Sequence analysis of a 237 kb genomic fragment from the central region of the MHC has revealed that the HLA-B and HLA-C genes
are contained within duplicated segments peri-B (53 kb) and peri-C (48 kb), respectively, and separated by an intervening
sequence (IF) of 30 kb. The peri-B and peri-C segments share at least 90% sequence homology except when interrupted by insertions/deletions
including Alu, L1, an endogenous retrovirus, and pseudogenes. The sequences of peri-B, IF, and peri-C were searched for the
presence of Alu elements to use as markers of evolution, chromosomal rearrangements, and polymorphism. Of 29 Alu elements,
14 were identified in peri-B, 11 in peri-C, and 4 in IF. The Alu elements in peri-B and peri-C clustered phylogenetically
into two clades which were classified as ``preduplication' and ``postduplication' clades. Four Alu J elements that are shared
by peri-B and peri-C and are flanked by homologous sequences in their paralogous locations, respectively, clustered into a
``preduplication' clade. By contrast, the majority of Alu elements, which are unique to either peri-B or peri-C, clustered
into a postduplication clade together with the Alu consensus subfamily members ranging from platyrrhine-specific (Spqxcg)
to catarrhine-specific Alu sequences (Y). The insertion of platyrrhine-specific Alu elements in postduplication locations
of peri-B and peri-C implies that these two segments are the products of a duplication which occurred in primates prior to
the divergence of the New World primate from the human lineage (35–44 mya). Examination of the paralogous Alu integration
sites revealed that 9 of 14 postduplication Alu sequences have produced microsatellites of different length and sequence within
the Alu 3′-poly A tail. The present analysis supports the hypothesis that HLA-B and HLA-C genes are products of an extended
segmental duplication between 44 and 81 million years ago (mya), and that subsequent diversification of both genomic segments
occurred because of the mobility and mutation of retroelements such as Alu repeats.
Received: 21 May 1997 / Accepted: 9 July 1997 相似文献
143.
144.
Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V. 总被引:1,自引:0,他引:1 下载免费PDF全文
J Michaud G N Thompson L C Brody G Steel C Obie G Fontaine K Schappert C G Keith D Valle G A Mitchell 《American journal of human genetics》1995,56(3):616-622
We discovered the missense mutation, A226V, in the ornithine-delta-aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported. 相似文献
145.
Andrew M. Jackson Anton B. Alexandrov S. Prescott Keith James 《Cancer immunology, immunotherapy : CII》1995,40(2):119-124
Intravesical immunotherapy for bladder cancer is the most effective form of tumour immunotherapy. Following repeated instillations
of bacillus Calmette-Guérin (BCG) organisms into the bladder large 0quantities of several cytokines are detected in the urine.
These cytokines include interleukins IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, tumour necrosis factor α (TNFα), interferon γ (IFNγ)
and also soluble intercellular adhesion molecule ICAM-1. In the work reported here we simultaneously quantified urinary levels
of TNFα, TNFβ, TNF receptor I and TNF receptor II by enzyme-linked immunosorbent assay (ELISA) techniques and compared this
with bioactive levels of TNF. This was undertaken with a limited number of patients throughout a course of six instillations
of immuno therapy. Sequential instillations of BCG induced secretion of TNFα and TNFβ into urine. These cytokines were not
always secreted simultaneously, perhaps suggesting differential regulation of their synthesis. Maximal concentrations of TNFα
were 675 pg/ml and TNFβ 47 pg/ml. High levels of both species of soluble TNF receptor were readily identified in urine. Maximal
levels of sTNF-RI were 6200 pg/ml (range from 0) and for sTNF-RII 7800 pg/ml (range from 0). Contrasting with earlier published
observations concerning cytokine levels, the concentration of soluble receptor did not increase with repeated instillation.
In apparent contrast with the ELISA data, very low levels of bioactive TNF were identified by the L929 bioassay (maximum concentration
1 U/ml) despite the elevated concen t ration of immunoreactive TNF. The large concentrations of soluble TNF receptor in patients’
urine samples could account for the apparently low bioactivity as determined by the L929 cytotoxicity assay. The precise nature
of the role of TNF in BCG immunotherapy remains undetermined; however, it is thought that proinflammatory cytokines are in
part responsible for the clinical efficacy of this therapeutic approach. Whether other cytokines are antogonised by soluble
binding proteins remains to be determined. Furthermore, whether TNF is bioactive in the bladder wall and only neutralised
in the urine also requires investigation.
Received: 24 August 1994 / Accepted: 17 October 1994 相似文献
146.
Keith L. Constantine Mark S. Friedrichs David Detlefsen Maki Nishio Mitsuaki Tsunakawa Tamotsu Furumai Hiroaki Ohkuma Toshikazu Oki Susan Hill Robert E. Bruccoleri Pin-Fang Lin Luciano Mueller 《Journal of biomolecular NMR》1995,5(3):271-286
Summary The 21-amino acid peptides siamycin II (BMY-29303) and siamycin I (BMY-29304), derived from Streptomyces strains AA3891 and AA6532, respectively, have been found to inhibit HIV-1 fusion and viral replication in cell culture. The primary sequence of siamycin II is CLGIGSCNDFAGCGYAIVCFW. Siamycin I differs by only one amino acid; it has a valine residue at position 4. In both peptides, disulfide bonds link Cys1 with Cys13 and Cys7 with Cys19, and the side chain of Asp9 forms an amide bond with the N-terminus. Siamycin II, when dissolved in a 50:50 mixture of DMSO and H2O, yields NOESY spectra with exceptional numbers of cross peaks for a peptide of this size. We have used 335 NOE distance constraints and 13 dihedral angle constraints to generate an ensemble of 30 siamycin II structures; these have average backbone atom and all heavy atom rmsd values to the mean coordinates of 0.24 and 0.52 Å, respectively. The peptide displays an unusual wedge-shaped structure, with one face being predominantly hydrophobic and the other being predominantly hydrophilic. Chemical shift and NOE data show that the siamycin I structure is essentially identical to siamycin II. These peptides may act by preventing oligomerization of the HIV transmembrane glycoprotein gp41, or by interfering with interactions between gp41 and the envelope glycoprotein gp120, the cell membrane or membrane-bound proteins [Frèchet, D. et al. (1994) Biochemistry, 33, 42–50]. The amphipathic nature of siamycin II and siamycin I suggests that a polar (or apolar) site on the target protein may be masked by the apolar (or polar) face of the peptide upon peptide/protein complexation.Abbreviations ABNR
adopted basis Newton Raphson
- AIDS
acquired immunodeficiency syndrome
- CW
continuous wave
- DMSO
dimethylsulfoxide
- DQF-COSY
two-dimensional double-quantum-filtered correlation spectroscopy
- HIV
human immunodeficiency virus
- HSQC
heteronuclear single-quantum coherence
- NOE
nuclear Overhauser enhancement
- NOESY
two-dimensional nuclear Overhauser enhancement spectroscopy
- ppm
parts per million
- P.E.-COSY
two-dimensional primitive exclusive correlation spectroscopy
- REDAC
redundant dihedral angle constraint
- rf
radio frequency
- rmsd
root-mean-square difference
- SIV
simian immunodeficiency virus
- sw
spectral width
- m
mixing time
- TOCSY
two-dimensional total correlation spectroscopy
- TSP
trimethylsilyl-2,2,3,3-2H4-propionate
- 2D
two-dimensional 相似文献
147.
Mimi Tanimoto Keith Roberts Liam Dolan 《The Plant journal : for cell and molecular biology》1995,8(6):943-948
Evidence is provided that ethylene is a positive regulator of hair cell development in the root epidermis of Arabidopsis thaliana. Treatment of seedlings with increasing concentrations of the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC) results in progressively more root hair cells developing in positions normally occupied by non-hair cells. Consistent with these findings are observations that treatments that block either ethylene synthesis or its perception reduce the number of root hairs. A model is proposed in which either ethylene or ACC is a signal involved in specifying the pattern of cell differentiation in the Arabidopsis root epidermis. 相似文献
148.
Nicola J. Stacey Keith Roberts Nicholas C. Carpita Brian Wells Maureen C. McCann 《The Plant journal : for cell and molecular biology》1995,8(6):891-906
The Zinnia mesophyll cell system consists of isolated leaf mesophyll cells in culture that can be induced, by auxin and cytokinin, to transdifferentiate semi-synchronously into tracheary elements (TEs). This system has been used to establish the precise time point at which the TE cell fate becomes determined, and then changes have been looked for in cell-wall composition and architecture that are associated with the establishment of competence, determination, and differentiation with the transition from primary to secondary cell wall formation. At very early stages in this time course, changes in the repertoire of proteins and polysaccharides both in the cell wall and secreted into the culture medium were found. Changes in the secretion of pectic polysaccharides, xyloglucans and arabinogalactan proteins (AGPs) have been detected using the monoclonal antibodies JIM 7, CCRC-M1 and JIM 13, that recognize these three classes of cell-wall molecule, respectively. Twenty-four hours before secondary thickenings are visible, an AGP is present in the primary walls of a subpopulation of cells, and is secreted into the culture medium. This molecule is present in the secondary thickenings of mature TEs but not in their surrounding primary walls. Methyl-esterified pectic polysaccharides are present in all cell walls and are secreted into the culture medium throughout the time course of differentiation, though at an increased rate in inductive medium. However, sugar and linkage analysis of culture media shows that a relatively unbranched rhamnogalacturonan is enriched in inductive medium around the time of determination and increases rapidly in concentration. The amount of fucosylated xyloglucan in cell walls increases during the time course, but appears in inductive medium 24 h earlier than in control medium and may have a subtly different structure. The fucose-containing epitope on the xyloglucan disappears abruptly and entirely from inductive medium 6 h before any secondary thickenings are visible in the cells. The disappearance of the epitope is correlated with secretion of several hydrolytic enzyme activities. In Zinnia leaves, the mesophyll cell walls contain neither the fucosylated xyloglucan nor the AGP, although methylesterified pectin is present. All three epitopes are expressed in the vascular bundles, and the AGP is specifically localized in the xylem cells. Fucosylated xyloglucan is also present in the epidermal tissue, and the AGP is present in guard cells. The dynamic behaviour of these specific cell-wall molecules is tightly correlated with differentiation events in vitro, and can be clearly distinguished from the production of new wall material found in expanding and elongating cells. The precise timing of the appearance and disappearance of these proteins and polysaccharides compared with the point of cell-fate determination provides us with a series of cell-surface markers for cell states at very early times in the transdifferentiation pathway. 相似文献
149.
150.
An algorithm for nucleic acid and protein sequence alignment is presented. It is a non-metric local similarity minimal-difference
algorithm and in the current implementation, assembles the matching regions found into a pseudo-global format. Its strengths
are its speed of execution and the especially convenient presentation of its output. The algorithm is intended for use in
sequence melding and local (small-region) similarity searching. It is not designed to replace a metric Needleman-Wunsch-Sellers-type
similarity algorithm. The program is written in FORTRAN and is designed to be easily transportable to a variety of computer
systems. 相似文献