全文获取类型
收费全文 | 43104篇 |
免费 | 131篇 |
国内免费 | 151篇 |
专业分类
系统科学 | 330篇 |
丛书文集 | 868篇 |
教育与普及 | 79篇 |
理论与方法论 | 142篇 |
现状及发展 | 19131篇 |
研究方法 | 1643篇 |
综合类 | 20440篇 |
自然研究 | 753篇 |
出版年
2013年 | 299篇 |
2012年 | 575篇 |
2011年 | 1329篇 |
2010年 | 240篇 |
2008年 | 681篇 |
2007年 | 820篇 |
2006年 | 779篇 |
2005年 | 812篇 |
2004年 | 861篇 |
2003年 | 764篇 |
2002年 | 739篇 |
2001年 | 1259篇 |
2000年 | 1215篇 |
1999年 | 790篇 |
1992年 | 793篇 |
1991年 | 624篇 |
1990年 | 671篇 |
1989年 | 614篇 |
1988年 | 616篇 |
1987年 | 643篇 |
1986年 | 648篇 |
1985年 | 876篇 |
1984年 | 633篇 |
1983年 | 530篇 |
1982年 | 462篇 |
1981年 | 498篇 |
1980年 | 625篇 |
1979年 | 1374篇 |
1978年 | 1068篇 |
1977年 | 1027篇 |
1976年 | 858篇 |
1975年 | 914篇 |
1974年 | 1256篇 |
1973年 | 1068篇 |
1972年 | 1146篇 |
1971年 | 1304篇 |
1970年 | 1773篇 |
1969年 | 1384篇 |
1968年 | 1197篇 |
1967年 | 1240篇 |
1966年 | 1146篇 |
1965年 | 862篇 |
1964年 | 263篇 |
1959年 | 487篇 |
1958年 | 846篇 |
1957年 | 604篇 |
1956年 | 492篇 |
1955年 | 449篇 |
1954年 | 496篇 |
1948年 | 333篇 |
排序方式: 共有10000条查询结果,搜索用时 15 毫秒
901.
Several viral and bacterial live recombinant vaccine vehicles are being developed to produce a new generation of vaccines against a broad spectrum of infectious diseases. The human tuberculosis vaccine Mycobacterium bovis bacillus Calmette-Guerin (BCG) has features that make it a particularly attractive live recombinant vaccine vehicle. BCG and other mycobacteria are highly effective adjuvants, and the immune response to mycobacteria has been studied extensively. With nearly two billion immunizations, BCG has a long record of safe use in man. It is one of the few vaccines that can be given at birth, it engenders long-lived immune responses with only a single dose, and there is a worldwide distribution network with experience in BCG vaccination. Recently developed molecular genetic tools and methods for mycobacteria have provided the means to introduce foreign genes into BCG. Here we report that a variety of human immunodeficiency virus type 1 polypeptides can be expressed in BCG recombinants under the control of the mycobacterial hsp70 promoter and that the foreign polypeptides produced in BCG can induce antibody and T-cell responses. These results demonstrate that BCG can be used as a live recombinant vaccine vehicle to induce immune responses to pathogen proteins produced by the bacillus. 相似文献
902.
903.
A selective deficit for writing vowels in acquired dysgraphia 总被引:2,自引:0,他引:2
Brain-damaged patients with acquired writing disorders provide important information about the normal processes of spelling and writing. Current models indicate that to produce a letter string, its 'abstract' representation is computed and stored in a temporary orthographic buffer, from which it is converted to a verbal code (if the word is to be spelled aloud) or to a physical letter code (if the word is to be written). The stored graphemic representations specify the identity and order of the component letters and their consonant/vowel status. Here I describe the spelling performance of two patients with a selective deficit in writing vowels. When writing words, the first patient omitted all vowels, leaving a blank space between consonants or consonant clusters, whereas the second produced errors that almost exclusively involved vowels. This pattern of performance supports the hypothesis that the consonant/vowel status of graphemes is differentially specified in the spelling process and may be selectively affected after brain damage. 相似文献
904.
A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene 总被引:117,自引:0,他引:117
Of the various classes of antibodies that B lymphocytes can produce, class M (IgM) is the first to be expressed on the membrane of the developing cells. Pre-B cells, the precursors of B-lymphocytes, produce the heavy chain of IgM (mu chain), but not light chains. Recent data suggest that pre-B cells express mu chains on the membrane together with the 'surrogate' light chains lambda 5 and V pre B (refs 2-7). This complex could control pre-B-cell differentiation, in particular the rearrangement of the light-chain genes. We have now assessed the importance of the membrane form of the mu chain in B-cell development by generating mice lacking this chain. We disrupted one of the membrane exons of the gene encoding the mu-chain constant region by gene targeting in mouse embryonic stem cells. From these cells we derived mice heterozygous or homozygous for the mutation. B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation. 相似文献
905.
A coat subunit of Golgi-derived non-clathrin-coated vesicles with homology to the clathrin-coated vesicle coat protein beta-adaptin 总被引:76,自引:0,他引:76
T Serafini G Stenbeck A Brecht F Lottspeich L Orci J E Rothman F T Wieland 《Nature》1991,349(6306):215-220
Four high-molecular-weight proteins form the main subunits of the coat of Golgi-derived (non-clathrin) coated vesicles. One of these coat proteins, beta-COP, is identical to a Golgi-associated protein of relative mass 110,000 (110K) that shares homology with the adaptin proteins of clathrin-coated vesicles. This connection, and the comparable molecular weights of the coat proteins of Golgi-derived and clathrin-coated vesicles, indicates that they may be structurally related. The identification of beta-COP as the 110K protein explains the blocking of secretion by the drug brefeldin A. 相似文献
906.
A homologue of the bacterial heat-shock gene DnaJ that alters protein sorting in yeast 总被引:22,自引:0,他引:22
Heat-shock proteins have been implicated in assembly of protein complexes, correct protein folding and uptake of proteins into organelles. In Escherichia coli, the heat-shock protein DnaJ and the Hsp70 homologue, DnaK, act together to disassemble a protein complex involved in bacteriophage lambda replication. We report the identification of SCJ1, a gene in the yeast Saccharomyces cerevisiae that encodes a homologue of the bacterial DnaJ protein. SCJ1 was identified by a genetic screen in which increased expression of candidate genes results in missorting of a nuclear-targeted test protein. The predicted amino-acid sequence of SCJ1 is 37% identical to the entire E. coli DnaJ protein. Hybridization experiments indicate that there is a family of yeast genes related to SCJ1. These findings suggest that the Hsp70 DnaK-DnaJ interaction is general to eukaryotes. 相似文献
907.
New use of BCG for recombinant vaccines 总被引:147,自引:0,他引:147
C K Stover V F de la Cruz T R Fuerst J E Burlein L A Benson L T Bennett G P Bansal J F Young M H Lee G F Hatfull 《Nature》1991,351(6326):456-460
BCG, a live attenuated tubercle bacillus, is the most widely used vaccine in the world and is also a useful vaccine vehicle for delivering protective antigens of multiple pathogens. Extrachromosomal and integrative expression vectors carrying the regulatory sequences for major BCG heat-shock proteins have been developed to allow expression of foreign antigens in BCG. These recombinant BCG strains can elicit long-lasting humoral and cellular immune responses to foreign antigens in mice. 相似文献
908.
909.
A pseudoknot-like structure required for efficient self-cleavage of hepatitis delta virus RNA 总被引:41,自引:0,他引:41
Hepatitis delta virus genomic and antigenomic RNAs contain a self-cleavage site hypothesized to function in processing the viral RNA during replication. Self-cleavage requires only a divalent cation and is mediated at the genomic site by a sequence of less than 85 nucleotides. We propose that the genomic self-cleaving sequence element and a corresponding sequence from the anti-genomic RNA could generate related secondary structures. The region of the antigenomic sequence, predicted from the proposed structure, was synthesized and shown to be sufficient for self-cleavage. Evidence for two stems which form a tertiary interaction was obtained by site-specific mutagenesis of the antigenomic sequence. Efficient self-cleavage in 10 M formamide or 5 M urea, also a property of the genomic sequence, was dependent on base-pairing in both stems. But in the absence of denaturants, the stem distal to the site of cleavage was not required, suggesting that the tertiary interaction stabilizes the structure required for self-cleavage. 相似文献
910.
A novel cyclin encoded by a bcl1-linked candidate oncogene 总被引:145,自引:0,他引:145
T Motokura T Bloom H G Kim H Jüppner J V Ruderman H M Kronenberg A Arnold 《Nature》1991,350(6318):512-515
We have previously identified a candidate oncogene (PRAD1 or D11S287E) on chromosome 11q13 which is clonally rearranged with the parathyroid hormone locus in a subset of benign parathyroid tumours. We now report that a cloned human placental PRAD1 complementary DNA encodes a protein of 295 amino acids with sequence similarities to the cyclins. Cyclins can form a complex with and activate p34cdc2 protein kinase, thereby regulating progress through the cell cycle. PRAD 1 messenger RNA levels vary dramatically across the cell cycle in HeLa cells. Addition of the PRAD1 protein to interphase clam embryo lysates containing inactive p34cdc2 kinase and lacking endogenous cyclins allows it to be isolated using beads bearing p13suc1, a yeast protein that binds cdc2 and related kinases with high affinity and coprecipitates kinase-associated proteins. Addition of PRAD1 also induces phosphorylation of histone H1, a preferred substrate of cdc2. These data suggest that PRAD1 encodes a novel cyclin whose overexpression may play an important part in the development of various tumours with abnormalities in 11q13. 相似文献