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151.
T. Tvrdik Suzanne Marcus Sai-Mei Hou Susann Fält Peri Noori Natalia Podlutskaja Folker Hanefeld Petter Strømme Bo Lambert 《Human genetics》1998,103(3):311-318
Mutations identified in the hypoxanthine phosphoribosyltransferase (HPRT) gene of patients with Lesch-Nyhan (LN) syndrome
are dominated by simple base substitutions. Few hotspot positions have been identified, and only three large genomic rearrangements
have been characterized at the molecular level. We have identified one novel mutation, two tentative hot spot mutations, and
two deletions by direct sequencing of HPRT cDNA or genomic DNA from fibroblasts or T-lymphocytes from LN patients in five
unrelated families. One is a missense mutation caused by a 610C→T transition of the first base of HPRT exon 9. This mutation
has not been described previously in an LN patient. A nonsense mutation caused by a 508C→T transition at a CpG site in HPRT
exon 7 in the second patient and his younger brother is the fifth mutation of this kind among LN patients. Another tentative
hotspot mutation in the third patient, a frame shift caused by a G nucleotide insertion in a monotonous repeat of six Gs in
HPRT exon 3, has been reported previously in three other LN patients. The fourth patient had a tandem deletion: a 57-bp deletion
in an internally repeated Alu-sequence of intron 1 was separated by 14 bp from a 627-bp deletion that included HPRT exon 2 and was flanked by a 4-bp repeat.
This complex mutation is probably caused by a combination of homologous recombination and replication slippage. Another large
genomic deletion of 2969 bp in the fifth patient extended from one Alu-sequence in the promoter region to another Alu-sequence of intron 1, deleting the whole of HPRT exon 1. The breakpoints were located within two 39-bp homologous sequences,
one of which overlapped with a well-conserved 26-bp Alu-core sequence previously suggested as promoting recombination. These results contribute to the establishment of a molecular
spectrum of LN mutations, support previous data indicating possible mutational hotspots, and provide evidence for the involvement
of Alu-mediated recombination in HPRT deletion mutagenesis.
Received: 21 April 1998 / Accepted: 16 July 1998 相似文献
152.
Trophodynamics and functional feeding groups of North Sea fauna: a combined stable isotope and fatty acid approach 总被引:1,自引:0,他引:1
Benjamin Kürten Inmaculada Frutos Ulrich Struck Suzanne J. Painting Nicholas V. C. Polunin Jack J. Middelburg 《Biogeochemistry》2013,113(1-3):189-212
The trophodynamics of pelagic and benthic animals of the North Sea, North Atlantic shelf, were assessed using stable isotope analysis (SIA) of natural abundance carbon and nitrogen isotopes, lipid fingerprinting and compound-specific SIA (CSIA) of phospholipid-derived fatty acids (PLFAs). Zooplankton (z), epi- and supra-benthic macrofauna were collected in the Southern Bight, at the Oyster Grounds and at North Dogger, 111 km north of the Dogger Bank. The study included 22 taxonomic groups with particular reference to Mollusca (Bivalvia and Gastropoda) and Crustacea. Primary consumers (Bivalvia) were overall most 15N enriched in the southern North Sea (6.1‰) and more depleted in the Oyster Grounds (5.5‰) and at North Dogger (2.8‰) demonstrating differences in isotopic baselines for bivalve fauna between the study sites. Higher trophic levels also followed this trend. Over an annual cycle, consumers tended to exhibit 15N depletion during spring followed by 15N enriched signatures in autumn and winter. The observed seasonal changes of δ 15N were more pronounced for suspension feeders and deposit feeders (dfs) than for filter feeders (ffs). The position of animals in plots of δ 13C and δ 15N largely concurred with the expected position according to literature-based functional feeding groups. PLFA fingerprints of groups such as z were distinct from benthic groups, e.g. benthic ffs and dfs, and predatory macrobenthos. δ 13CPLFA signatures indicated similarities in 13C moiety sources that constituted δ 13CPLFA. Although functional groups of pelagic zooplankton and (supra-) benthic animals represented phylogenetically distinct consumer groups, δ 13CPLFA demonstrated that both groups were supported by pelagic primary production and relied on the same macronutrients such as PLFAs. Errors related to the static categorization of small invertebrates into fixed trophic positions defined by phylogenetic groupings rather than by functional feeding groups, and information on seasonal trophodynamic variability, may have implications for the reliability of numerical marine ecosystem models. 相似文献
153.
Davies A Kalb S Liang B Aldrich CJ Lemonnier FA Jiang H Cotter R Soloski MJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,170(10):5027-5033
The MHC class Ib molecule Qa-1 binds specifically and predominantly to a single 9-aa peptide (AMAPRTLLL) derived from the leader sequence of many MHC class Ia proteins. This peptide is referred to as Qdm. In this study, we report the isolation and sequencing of a heat shock protein 60-derived peptide (GMKFDRGYI) from Qa-1. This peptide is the dominant peptide bound to Qa-1 in the absence of Qdm. A Qa-1-restricted CTL clone recognizes this heat shock protein 60 peptide, further verifying that it binds to Qa-1 and a peptide from the homologous Salmonella typhimurium protein GroEL (GMQFDRGYL). These observations have implications for how Qa-1 can influence NK cell and T cell effector function via the TCR and CD94/NKG2 family members, and how this effect can change under conditions that cause the peptides bound to Qa-1 to change. 相似文献
154.
Wendy Blay Puryear Hisashi Akiyama Suzanne D. Geer Nora P. Ramirez Xinwei Yu Bj?rn M. Reinhard Suryaram Gummuluru 《PLoS pathogens》2013,9(4)
Human immunodeficiency virus type 1 (HIV-1) interactions with myeloid dendritic cells (DCs) can result in virus dissemination to CD4+ T cells via a trans infection pathway dependent on virion incorporation of the host cell derived glycosphingolipid (GSL), GM3. The mechanism of DC-mediated trans infection is extremely efficacious and can result in infection of multiple CD4+ T cells as these cells make exploratory contacts on the DC surface. While it has long been appreciated that activation of DCs with ligands that induce type I IFN signaling pathway dramatically enhances DC-mediated T cell trans infection, the mechanism by which this occurs has remained unclear until now. Here, we demonstrate that the type I IFN-inducible Siglec-1, CD169, is the DC receptor that captures HIV in a GM3-dependent manner. Selective downregulation of CD169 expression, neutralizing CD169 function, or depletion of GSLs from virions, abrogated DC-mediated HIV-1 capture and trans infection, while exogenous expression of CD169 in receptor-naïve cells rescued GSL-dependent capture and trans infection. HIV-1 particles co-localized with CD169 on DC surface immediately following capture and subsequently within non-lysosomal compartments that redistributed to the DC – T cell infectious synapses upon initiation of T cell contact. Together, these findings describe a novel mechanism of pathogen parasitization of host encoded cellular recognition machinery (GM3 – CD169 interaction) for DC-dependent HIV dissemination. 相似文献
155.
Monika M. Lulsdorf Hai Ying Yuan Susan M. H. Slater Albert Vandenberg Xiumei Han L. Irina Zaharia Suzanne R. Abrams 《Plant Growth Regulation》2013,71(2):191-198
Cicer anatolicum, a perennial species, has ascochyta blight resistance superior to that found in the cultivated chickpea. However, hybridization barriers during early stages of embryo development curtail access to this trait. Since hormones play an essential role in early embryo development, we have determined the hormone profiles of 4-, 8-, and 12-day old seeds from a Canadian chickpea (Cicer arietinum L.) cv. CDC Xena, from Indian cvs. Swetha and Bharati, and from a perennial accession of C. anatolicum (PI 383626). Indole-3-acetic acid content peaked on day 4 in CDC Xena, on day 8 in both Indian cultivars but only on day 12 in C. anatolicum. The cytokinins, isopentenyladenosine (iPA) and trans zeatin riboside (tZR) were predominant in CDC Xena and Swetha seeds on day 4, whereas cis zeatin riboside was the major component in Bharati. In C. anatolicum, iPA maxed out on day 4 and tZR on day 12. The bioactive gibberellin GA1 spiked on day 4 in CDC Xena and Bharati, on day 8 in Swetha but only on day 12 in C. anatolicum. Eight-day old seeds had the highest abscisic acid content in the cultivars but spiked on day 12 in the perennial species. The hormone profiles of the perennial species showed delayed spikes in all four hormone groups indicating that there is a mismatch in the hormone requirements of the different embryos. Improving synchronization of early seed hormone profiles of cultivated and perennial chickpea should improve interspecific hybrid production. 相似文献
156.
Insulin inhibits PDGF-directed VSMC migration via NO/ cGMP increase of MKP-1 and its inactivation of MAPKs 总被引:9,自引:0,他引:9
Jacob A Molkentin JD Smolenski A Lohmann SM Begum N 《American journal of physiology. Cell physiology》2002,283(3):C704-C713
In this study, we examined the roleof insulin in the control of vascular smooth muscle cell (VSMC)migration in the normal vasculature. Platelet-derived growth factor(PDGF) increased VSMC migration, which was inhibited by pretreatmentwith insulin in a dose-dependent manner. Insulin also caused a 60%decrease in PDGF-stimulated mitogen-activated protein kinase (MAPK)phosphorylation and activation. Insulin inhibition of MAPK wasaccompanied by a rapid induction of MAPK phosphatase (MKP-1), whichinactivates MAPKs by dephosphorylation. Pretreatment with inhibitors ofthe nitric oxide (NO)/cGMP pathway, blocked insulin-induced MKP-1 expression and restored PDGF-stimulated MAPK activation and migration. In contrast, adenoviral infection of VSMCs with MKP-1 or cGMP-dependent protein kinase I (cGK I), the downstream effector of cGMPsignaling, blocked the activation of MAPK and prevented PDGF-directedVSMC migration. Expression of antisense MKP-1 RNA prevented insulin's inhibitory effect and restored PDGF-directed VSMC migration and MAPKphosphorylation. We conclude that insulin inhibition of VSMC migrationmay be mediated in part by NO/cGMP/cGK I induction of MKP-1 andconsequent inactivation of MAPKs. 相似文献
157.
The Accelerated Failure Time Model Under Biased Sampling 总被引:1,自引:0,他引:1
Summary Chen (2009, Biometrics) studies the semi‐parametric accelerated failure time model for data that are size biased. Chen considers only the uncensored case and uses hazard‐based estimation methods originally developed for censored observations. However, for uncensored data, a simple linear regression on the log scale is more natural and provides better estimators. 相似文献
158.
Ward AJ Duff AJ Horsfall JS Currie S 《Proceedings. Biological sciences / The Royal Society》2008,275(1630):101-105
Chemical cues are of enormous importance in mediating the behaviour of animals, enabling them to navigate throughout their habitats, to detect the presence of predators or prey and for social recognition-identifying and discriminating between conspecifics. In many species of freshwater fish, social recognition is known to be based primarily on chemical cues. Such recognition mechanisms are vulnerable to disruption by the presence of anthropogenic contaminants in the aquatic environment. Here we show that acute exposure to low, environmentally relevant dosages of the ubiquitous contaminant, 4-nonylphenol, can seriously affect social recognition and ultimately social organization in fishes. A 1 hour 0.5 microgl-1 dose was sufficient to alter the response of members of a shoaling fish species (juvenile banded killifish, Fundulus diaphanus) to conspecific chemical cues. Dosages of 1-2 microgl-1 caused killifish to orient away from dosed conspecifics, in both a flow channel and an arena. Given the overall importance of shoaling as an adaptive strategy against predators and for locating food, it is likely that its disruption by anthropogenic contaminants would have serious implications for fishes' fitness. 相似文献
159.
Amphiphilic and Nonamphiphilic Forms of Torpedo Cholinesterases: I. Solubility and Aggregation Properties 总被引:3,自引:3,他引:3
Suzanne Bon Jean-Pierre Toutant† Khaled Méflah † Jean Massoulié 《Journal of neurochemistry》1988,51(3):776-785
We report an analysis of the solubility and hydrophobic properties of the globular forms of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) from various Torpedo tissues. We distinguish globular nonamphiphilic forms (Gna) from globular amphiphilic forms (Ga). The Ga forms bind micelles of detergent, as indicated by the following properties. They are converted by mild proteolysis into nonamphiphilic derivatives. Their Stokes radius in the presence of Triton X-100 is approximately 2 nm greater than that of their lytic derivatives. The G2a forms fall in two classes. Class I contains molecules that aggregate in the absence of detergent, when mixed with an AChE-depleted Triton X-100 extract from electric organ. AChE G2a forms from electric organs, nerves, skeletal muscle, and erythrocyte membranes correspond to this type, which is also detectable in detergent-soluble (DS) extracts of electric lobes and spinal cord. Class II forms never aggregate but only present a slight shift in sedimentation coefficient, in the presence or absence of detergent. This class contains the AChE G2a forms of plasma and of the low-salt-soluble (LSS) fractions from spinal cord and electric lobes. The heart possesses a BuChE G2a form of class II in LSS extracts, as well as a similar G1a form. G4a forms of AChE, which are solubilized only in the presence of detergent and aggregate in the absence of detergent, represent a large proportion of cholinesterase in DS extracts of nerves and spinal cord, together with a smaller component of G4a BuChE. These forms may be converted to nonamphiphilic derivatives by Pronase. Nonaggregating G4a forms exist at low levels in the plasma (BuChE) and in LSS extracts of nerves (BuChE) and spinal cord (AChE). 相似文献
160.
Dryden KA Tihova M Nowotny N Matsui SM Mendez E Yeager M 《Journal of molecular biology》2012,422(5):650-658
Human astroviruses (HAstVs) are a major cause of gastroenteritis. HAstV assembles from the structural protein VP90 and undergoes a cascade of proteolytic cleavages. Cleavage to VP70 is required for release of immature particles from cells, and subsequent cleavage by trypsin confers infectivity. We used electron cryomicroscopy and icosahedral image analysis to determine the first experimentally derived, three-dimensional structures of an immature VP70 virion and a fully proteolyzed, infectious virion. Both particles display T = 3 icosahedral symmetry and nearly identical solid capsid shells with diameters of ~ 350 Å. Globular spikes emanate from the capsid surface, yielding an overall diameter of ~ 440 Å. While the immature particles display 90 dimeric spikes, the mature capsid only displays 30 spikes, located on the icosahedral 2-fold axes. Loss of the 60 peripentonal spikes likely plays an important role in viral infectivity. In addition, immature HAstV bears a striking resemblance to the structure of hepatitis E virus (HEV)-like particles, as previously predicted from structural similarity of the crystal structure of the astrovirus spike domain with the HEV P-domain [Dong, J., Dong, L., Méndez, E. &; Tao, Y. (2011). Crystal structure of the human astrovirus capsid spike. Proc. Natl. Acad. Sci. USA 108, 12681–12686]. Similarities between their capsid shells and dimeric spikes and between the sequences of their capsid proteins suggest that these viral families are phylogenetically related and may share common assembly and activation mechanisms. 相似文献