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991.
Miguel Angel Pujana Monica Gratacós Jordi Corral Isabel Banchs Aurora Sánchez David Genís Carlos Cervera Víctor Volpini X. Estivill 《Human genetics》1997,101(1):18-21
Genetic anticipation – increasing severity and a decrease in the age of onset with successive generations of a pedigree –
is clearly present in autosomal dominant cerebellar ataxia (ADCA). Anticipation is correlated with expansion of the CAG/CTG
repeat sequence to sizes above those in the normal range through the generations of a pedigree. Genetic heterogeneity has
been demonstrated for ADCA, with four cloned genes (SCA1, SCA2, SCA3/MJD, and SCA6) and three mapped loci (SCA4, SCA5 and
SCA7). Another related dominant ataxia, dentatorubral-pallidoluysian atrophy (DRPLA), presents anticipation with CAG/CTG repeat
expansions. We had previously analysed ADCA patients who had not shown repeat expansions in cloned genes for CAG/CTG repeat
expansions by the repeat expansion detection method (RED) and had detected expansions of between 48 and 88 units in 17 unrelated
familial cases. We present here an analysis of 13 genes and expressed sequence tags (ESTs) containing 10 or more CAG/ CTG
repeat sequences selected from public databases in the 17 unrelated ADCA patients. Of the 13 selected genes and ESTs, 9 were
found to be polymorphic with heterozygosities ranging between 0.09 and 0.80 and 2 to 17 alleles. In ADCA patients none of
the loci showed expansions above the normal range of the CAG/CTG repeat sequences, excluding them as the mutation causing
ADCA.
Received: 28 May 1997 / Accepted: 30 June 1997 相似文献
992.
Neural correlates of behavioral gap detection in the inferior colliculus of the young CBA mouse 总被引:6,自引:0,他引:6
J. P. Walton R. D. Frisina J. R. Ison W. E. O'Neill 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1997,181(2):161-176
The gap detection paradigm is frequently used in psychoacoustics to characterize the temporal acuity of the auditory system.
Neural responses to silent gaps embedded in white-noise carriers, were obtained from mouse inferior colliculus (IC) neurons
and the results compared to behavioral estimates of gap detection. Neural correlates of gap detection were obtained from 78
single neurons located in the central nucleus of the IC. Minimal gap thresholds (MGTs) were computed from single-unit gap
functions and were found to be comparable, 1–2 ms, to the behavioral gap threshold (2 ms). There was no difference in MGTs
for units in which both carrier intensities were collected. Single unit responses were classified based on temporal discharge
patterns to steady-state noise bursts. Onset and primary-like units had the shortest mean MGTs (2.0 ms), followed by sustained
units (4.0 ms) and phasic-off units (4.2 ms). The longest MGTs were obtained for inhibitory neurons (xˉ = 14 ms). Finally,
the time-course of behavioral and neurophysiological gap functions were found to be in good agreement. The results of the
present study indicate the neural code necessary for behavioral gap detection is present in the temporal discharge patterns
of the majority of IC neurons.
Accepted: 6 February 1997 相似文献
993.
994.
E. Breierová 《Letters in applied microbiology》1997,25(4):254-256
Six extracellular yeast glycoproteins were prepared from three yeast species in osmoticequilibrium and unequilibrium environments and used as non-penetrating cryoadditives. Theglycoprotein secreted by the strain Dipodascus australiensis into the growth mediumcontaining NaCl (8% w/v) was found to be the most effective cryoadditive. It was possible to usethis glycoprotein alone (without penetrating agent DMSO) for the cryoprotection of the yeastsstudied. 相似文献
995.
996.
Y. Z. Ziylan J. M. Lefauconnier G. Bernard J. M. Bourre 《Journal of neurochemistry》1989,52(3):684-689
The effect of dexamethasone administration and withdrawal was studied with respect to blood-brain barrier function. The tracers alpha-[3H]aminoisobutyric acid (AIB) (MW 104) and [14C]sucrose (MW 342), which have a low permeability across the intact endothelium, were simultaneously injected intravenously in rats treated with dexamethasone and placebo-treated control animals or in rats in which dexamethasone treatment was discontinued 3 days before the experiment. Unidirectional transfer constants (Ki) were determined in discrete brain regions. Steroid administration reduced the rate of influx of AIB and sucrose, whereas discontinuation of drug resulted in an increased permeability. These findings suggest that when exposure to glucocorticoids is prolonged, the efficiency of medical treatment of CNS diseases may decrease due to reduction of drug delivery to CNS. Thus, these experimental findings may have particular importance in the clinical setting of drug administration when considering the combination of steroids with other drugs, and may aid in understanding better the pathogenesis of some types of brain edema seen in patients from whom corticosteroid therapy has been withdrawn. 相似文献
997.
M. N. Collinson Andrew M. Fisher Jean Walker Jane Currie Lisa Williams Paul Roberts 《Human genetics》1997,101(2):175-180
We present 33 families in which a pericentric inversion of chromosome 10 is segregating. In addition, we summarise the data
on 32 families in which an apparently identical inv(10) has been reported in the literature. Ascertainment was through prenatal
diagnosis or with a normal phenotype in 21/33 families. In the other 12 families, probands were ascertained through a wide
variety of referral reasons but in all but one case (a stillbirth), studies of the family showed that the reason for referral
was unrelated to the chromosome abnormality. There has been, to our knowledge, no recorded instance of a recombinant chromosome
10 arising from this inversion and no excess of infertility or spontaneous abortion among carriers of either sex. We propose
that inv(10)(p11.2q21.2) can be regarded as a variant analogous to the pericentric inversion of chromosome 2(p11q13). We conclude
that prenatal chromosome analysis is not justified for inv(10) carriers. In addition, family investigation of carrier status
is not warranted in view of the unnecessary concern this may cause parents and other family members.
Received: 7 July 1997 / Accepted: 4 August 1997 相似文献
998.
Shigeaki Nonoyama Mitsunobu Shimadzu Hano Toru Kuniaki Seyama Hiroyuki Nunoi Michael Neubauer Jun-ichi Yata Hans D. Ochs 《Human genetics》1997,99(5):624-627
X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency caused by a defective CD40 ligand. We identified mutations
of the CD40 ligand gene in 13 unrelated Japanese XHIM patients. Of the four patients with missense mutations, one had a mutation
within the transmembrane domain, and the three others had mutations affecting the TNF homology region of the extracellular
domain. Two of the missense mutations resulted in the substitution of amino acids that are highly conserved in TNF family
proteins. Three patients had nonsense mutations, all of which resulted in the truncation of the TNF homology domain of the
CD40 ligand. Three patients had genomic DNA deletions of 2, 3 or 4 nucleotides, respectively. All of the deletions were flanked
by direct repeat sequences, suggesting that these deletions were caused by slipped mispairing. Three patients had mutations
within introns resulting in altered splicing, and multiple splicing products were found in one patient. Thus, each of the
13 Japanese patients had different mutations, 9 of them being novel mutations. These results indicate that mutations in XHIM
are highly heterogeneous, although codon 140 seems to be a hot spot of the CD40 ligand gene since two additional point mutations
were located at Trp 140, bringing the total numbers of mutations affecting codon 140 to six. In one XHIM family with a missense
mutation, prenatal diagnosis was performed by single-strand conformation polymorphism analysis of genomic DNA of a male fetus.
Received: 20 August 1996 相似文献
999.
The Huntington’s disease mutation has been identified as a CAG/polyglutamine repeat expansion in a large gene of unknown
function. In order to develop the transgenic systems necessary to uncover the molecular pathology of this disorder, it is
necessary to be able to manipulate highly expanded CAG repeats in a cloned form. We have identified a patient with an expanded
allele of greater than 170 repeat units and have cloned the mutant allele in the lambda zap vector. The recovery of highly
expanded repeats after clone propagation was more efficient when repeats were maintained as lambda phage clones rather than
as the plasmid counterparts. Manipulation of the repeats as phage clones has enabled us to generate Huntington’s disease transgenic
mice that contain highly expanded (CAG)115–(CAG)150 repeats and that develop a progressive neurological phenotype.
Received: 7 October 1996 / Revised: 5 December 1996 相似文献
1000.
M. Hakoda Naoyuki Kamatani Sakura Kurumada Yuko Hirai Kimitaka Sakamoto Hisashi Yamanaka Chihiro Terai Sadao Kashiwazaki 《Human genetics》1997,99(2):164-170
Both germline and somatic mutations are known to affect phenotypes of human cells in vivo. In previous studies, we cloned
mutant peripheral blood T cells from germline heterozygous humans for adenine phosphoribosyltransferase (APRT) (EC 2.4.2.7)
deficiency and found that approximately 1.3 × 10–4 peripheral T cells had undergone in vivo somatic mutations. Loss of heterozygosity (LOH) was the major cause of the mutations
at the APRT locus since approximately 80% of the mutant T cell clones exhibited loss of normal alleles. In the present study,
we identified three heterozygous individuals for APRT deficiency (representing two separate families), in whom none of the
somatic mutant cells exhibited LOH at the APRT locus. The germline mutant APRT alleles of these heterozygotes from two unrelated
families had the same gross DNA abnormalities detectable by Southern blotting. None of the germline mutant APRT alleles so
far reported had such gross DNA abnormalities. The data suggest that the germline mutation unique to these heterozygous individuals
is associated with the abrogation of LOH in somatic cells. The absence of LOH at a different locus has already been reported
in vitro in an established cell line but the present study describes the first such event in vivo in human individuals.
Received: 10 May 1996 相似文献