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121.
Amiot L Ferrone S Grosse-Wilde H Seliger B 《Cellular and molecular life sciences : CMLS》2011,68(3):417-431
Although the expression of the non-classical HLA class I molecule HLA-G was first reported to be restricted to the fetal–maternal
interface on the extravillous cytotrophoblasts, the distribution of HLA-G in normal tissues appears broader than originally
described. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic
lineage. More interestingly, under pathophysiological conditions HLA-G antigens may be expressed on various types of malignant
cells suggesting that HLA-G antigen expression is one strategy used by tumor cells to escape immune surveillance. In this
article, we will focus on HLA-G expression in cancers of distinct histology and its association with the clinical course of
diseases, on the underlying molecular mechanisms of impaired HLA-G expression, on the immune tolerant function of HLA-G in
tumors, and on the use of membrane-bound and soluble HLA-G as a diagnostic or prognostic biomarker to identify tumors and
to monitor disease stage, as well as on the use of HLA-G as a novel therapeutic target in cancer. 相似文献
122.
Pan Q Qiao F Gao C Norman B Optican L Zelenka PS 《Cellular and molecular life sciences : CMLS》2011,68(20):3425-3436
The non-receptor tyrosine kinase Src is a critical regulator of cytoskeletal contraction, cell adhesion, and migration. In
normal cells, Src activity is stringently controlled by Csk-dependent phosphorylation of Src(Y530), and by Cullin-5-dependent
ubiquitinylation, which affects active Src(pY419) exclusively, leading to its degradation by the proteosome. Previous work
has shown that Src activity is also limited by Cdk5, a proline-directed kinase, which has been shown to phosphorylate Src(S75).
Here we show that this phosphorylation promotes the ubiquitin-dependent degradation of Src, thus restricting the availability
of active Src. We demonstrate that Src(S75) phosphorylation occurs in vivo in epithelial cells, and like ubiquitinylation,
is associated only with active Src. Preventing Cdk5-dependent phosphorylation of Src(S75), by site-specific mutation of S75
or by Cdk5 inhibition or suppression, increases Src(Y419) phosphorylation and kinase activity, resulting in Src-dependent
cytoskeletal changes. In transfected cells, ubiquitinylation of Src(S75A) is about 35% that of wild-type Src-V5, and its half-life
is approximately 2.5-fold greater. Cdk5 suppression leads to a comparable decrease in the ubiquitinylation of endogenous Src
and a similar increase in Src stability. Together, these findings demonstrate that Cdk5-dependent phosphorylation of Src(S75)
is a physiologically significant mechanism of regulating intracellular Src activity. 相似文献
123.
Lubka-Pathak M Shah AA Gallozzi M Müller M Zimmermann U Löwenheim H Pfister M Knipper M Blin N Schimmang T 《Cellular and molecular life sciences : CMLS》2011,68(16):2739-2749
Introduction
Tff3 peptide exerts important functions in cytoprotection and restitution of the gastrointestinal (GI) tract epithelia. Moreover, its presence in the rodent inner ear and involvement in the hearing process was demonstrated recently. However, its role in the auditory system still remains elusive. Our previous results showed a deterioration of hearing with age in Tff3-deficient animals.Results
Present detailed analysis of auditory brain stem response (ABR) measurements and immunohistochemical study of selected functional proteins indicated a normal function and phenotype of the cochlea in Tff3 mutants. However, a microarray-based screening of tissue derived from the auditory central nervous system revealed an alteration of securin (Pttg1) and serpina3n expression between wild-type and Tff3 knock-out animals. This was confirmed by qRT-PCR, immunostaining and western blots.Conclusions
We found highly down-regulated Pttg1 and up-regulated serpina3n expression as a consequence of genetically deleting Tff3 in mice, indicating a potential role of these factors during the development of presbyacusis. 相似文献124.
Freinbichler W Colivicchi MA Stefanini C Bianchi L Ballini C Misini B Weinberger P Linert W Varešlija D Tipton KF Della Corte L 《Cellular and molecular life sciences : CMLS》2011,68(12):2067-2079
The so-called reactive oxygen species (ROS) are defined as oxygen-containing species that are more reactive than O(2) itself, which include hydrogen peroxide and superoxide. Although these are quite stable, they may be converted in the presence of transition metal ions, such as Fe(II), to the highly reactive oxygen species (hROS). hROS may exist as free hydroxyl radicals (HO·), as bound ("crypto") radicals or as Fe(IV)-oxo (ferryl) species and the somewhat less reactive, non-radical species, singlet oxygen. This review outlines the processes by which hROS may be formed, their damaging potential, and the evidence that they might have signaling functions. Since our understanding of the formation and actions of hROS depends on reliable procedures for their detection, particular attention is given to procedures for hROS detection and quantitation and their applicability to in vivo studies. 相似文献
125.
The demography of a population of Yarrow's spiny lizard, Sceloporus jarrovii , was examined from 2004 to 2006 in the canyon Las Piedras Encimadas, located in Gomez Palacio, Durango, México. Lizards were studied using a mark-recapture technique. Reproduction in females occurred between November and May, coinciding with dry conditions. Reproductive activity was highest (percent of females with vitellogenic follicles or embryos) in the middle of the dry season (November and December). Thirteen percent of females reached sexual maturity at an average age of 8.5 months. The population structure was similar in spring and fall, but not in summer. A notable feature of summer, coinciding with the wet season, was the greater number of hatchlings and juveniles. The overall sex ratio did not differ from 1:1. The density of adults varied from 12 to 62 animals ? 0.5 ha –1 . Temperate and arid-adapted populations of S. jarrovii exhibited broad similarity in timing of the reproductive season, whereas factors such as density, growth, age at sexual maturity, and survivorship differed. 相似文献
126.
Purdue MP Johansson M Zelenika D Toro JR Scelo G Moore LE Prokhortchouk E Wu X Kiemeney LA Gaborieau V Jacobs KB Chow WH Zaridze D Matveev V Lubinski J Trubicka J Szeszenia-Dabrowska N Lissowska J Rudnai P Fabianova E Bucur A Bencko V Foretova L Janout V Boffetta P Colt JS Davis FG Schwartz KL Banks RE Selby PJ Harnden P Berg CD Hsing AW Grubb RL Boeing H Vineis P Clavel-Chapelon F Palli D Tumino R Krogh V Panico S Duell EJ Quirós JR Sanchez MJ Navarro C Ardanaz E Dorronsoro M Khaw KT Allen NE 《Nature genetics》2011,43(1):60-65
127.
Becker-Heck A Zohn IE Okabe N Pollock A Lenhart KB Sullivan-Brown J McSheene J Loges NT Olbrich H Haeffner K Fliegauf M Horvath J Reinhardt R Nielsen KG Marthin JK Baktai G Anderson KV Geisler R Niswander L Omran H Burdine RD 《Nature genetics》2011,43(1):79-84
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous autosomal recessive disorder characterized by recurrent infections of the respiratory tract associated with the abnormal function of motile cilia. Approximately half of individuals with PCD also have alterations in the left-right organization of their internal organ positioning, including situs inversus and situs ambiguous (Kartagener's syndrome). Here, we identify an uncharacterized coiled-coil domain containing a protein, CCDC40, essential for correct left-right patterning in mouse, zebrafish and human. In mouse and zebrafish, Ccdc40 is expressed in tissues that contain motile cilia, and mutations in Ccdc40 result in cilia with reduced ranges of motility. We further show that CCDC40 mutations in humans result in a variant of PCD characterized by misplacement of the central pair of microtubules and defective assembly of inner dynein arms and dynein regulatory complexes. CCDC40 localizes to motile cilia and the apical cytoplasm and is required for axonemal recruitment of CCDC39, disruption of which underlies a similar variant of PCD. 相似文献
128.
Wright FA Strug LJ Doshi VK Commander CW Blackman SM Sun L Berthiaume Y Cutler D Cojocaru A Collaco JM Corey M Dorfman R Goddard K Green D Kent JW Lange EM Lee S Li W Luo J Mayhew GM Naughton KM Pace RG Paré P Rommens JM Sandford A Stonebraker JR Sun W Taylor C Vanscoy LL Zou F Blangero J Zielenski J O'Neal WK Drumm ML Durie PR Knowles MR Cutting GR 《Nature genetics》2011,43(6):539-546
A combined genome-wide association and linkage study was used to identify loci causing variation in cystic fibrosis lung disease severity. We identified a significant association (P = 3.34 × 10(-8)) near EHF and APIP (chr11p13) in p.Phe508del homozygotes (n = 1,978). The association replicated in p.Phe508del homozygotes (P = 0.006) from a separate family based study (n = 557), with P = 1.49 × 10(-9) for the three-study joint meta-analysis. Linkage analysis of 486 sibling pairs from the family based study identified a significant quantitative trait locus on chromosome 20q13.2 (log(10) odds = 5.03). Our findings provide insight into the causes of variation in lung disease severity in cystic fibrosis and suggest new therapeutic targets for this life-limiting disorder. 相似文献
129.
Gui Y Guo G Huang Y Hu X Tang A Gao S Wu R Chen C Li X Zhou L He M Li Z Sun X Jia W Chen J Yang S Zhou F Zhao X Wan S Ye R Liang C Liu Z Huang P Liu C Jiang H Wang Y Zheng H Sun L Liu X Jiang Z Feng D Chen J Wu S Zou J Zhang Z Yang R Zhao J Xu C Yin W Guan Z Ye J Zhang H Li J Kristiansen K Nickerson ML Theodorescu D Li Y Zhang X Li S Wang J Yang H Wang J Cai Z 《Nature genetics》2011,43(9):875-878
Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Here we sequenced the exomes of nine individuals with TCC and screened all the somatically mutated genes in a prevalence set of 88 additional individuals with TCC with different tumor stages and grades. In our study, we discovered a variety of genes previously unknown to be mutated in TCC. Notably, we identified genetic aberrations of the chromatin remodeling genes (UTX, MLL-MLL3, CREBBP-EP300, NCOR1, ARID1A and CHD6) in 59% of our 97 subjects with TCC. Of these genes, we showed UTX to be altered substantially more frequently in tumors of low stages and grades, highlighting its potential role in the classification and diagnosis of bladder cancer. Our results provide an overview of the genetic basis of TCC and suggest that aberration of chromatin regulation might be a hallmark of bladder cancer. 相似文献
130.
Matmati M Jacques P Maelfait J Verheugen E Kool M Sze M Geboes L Louagie E Mc Guire C Vereecke L Chu Y Boon L Staelens S Matthys P Lambrecht BN Schmidt-Supprian M Pasparakis M Elewaut D Beyaert R van Loo G 《Nature genetics》2011,43(9):908-912
A20 (TNFAIP3) is a protein that is involved in the negative feedback regulation of NF-κB signaling in response to specific proinflammatory stimuli in different cell types and has been suggested as a susceptibility gene for rheumatoid arthritis. To define the contribution of A20 to rheumatoid arthritis pathology, we generated myeloid-specific A20-deficient mice and show that specific ablation of Tnfaip3 in myeloid cells results in spontaneous development of a severe destructive polyarthritis with many features of rheumatoid arthritis. Myeloid-A20-deficient mice have high levels of inflammatory cytokines in their serum, consistent with a sustained NF-κB activation and higher TNF production by macrophages. Destructive polyarthritis in myeloid A20 knockout mice was TLR4-MyD88 and IL-6 dependent but was TNF independent. Myeloid A20 deficiency also promoted osteoclastogenesis in mice. Together, these observations indicate a critical and cell-specific function for A20 in the etiology of rheumatoid arthritis, supporting the idea of developing A20 modulatory drugs as cell-targeted therapies. 相似文献