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71.
M line-deficient titin causes cardiac lethality through impaired maturation of the sarcomere 下载免费PDF全文
Titin, the largest protein known to date, has been linked to sarcomere assembly and function through its elastic adaptor and signaling domains. Titin's M-line region contains a unique kinase domain that has been proposed to regulate sarcomere assembly via its substrate titin cap (T-cap). In this study, we use a titin M line-deficient mouse to show that the initial assembly of the sarcomere does not depend on titin's M-line region or the phosphorylation of T-cap by the titin kinase. Rather, titin's M-line region is required to form a continuous titin filament and to provide mechanical stability of the embryonic sarcomere. Even without titin integrating into the M band, sarcomeres show proper spacing and alignment of Z discs and M bands but fail to grow laterally and ultimately disassemble. The comparison of disassembly in the developing and mature knockout sarcomere suggests diverse functions for titin's M line in embryonic development and the adult heart that not only involve the differential expression of titin isoforms but also of titin-binding proteins. 相似文献
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We tested the survival potential and fitness of two different algae strains (the diatom Thalassiosira weissflogii and the cryptophyceae Rhodomonas sp.) under different growth conditions (complete darkness and short light intervals, simulating conditions in a deep mixed water column) at different temperatures, plus the effect of these conditions on the physiological fitness and growth after re-illumination was examined. Both species survived the experimental conditions without significant cell loss or physiological damage. Two different survival strategies were observed: (1) the diatom T. weissflogii immediately reduced its metabolic rate and stopped cell division. The effect on chlorophyll a (chl-a) content and photosynthetic capacity was negligible. At 10 °C, T. weissflogii used the short light windows to metabolize carbohydrates and growth. (2) The cryptophyte Rhodomonas sp. initially continued to grow after transfer into all trials. However, the cell number decreased after day 6. Carbohydrate and chl-a content went on to decrease dramatically (70 and 50%, respectively). After 3 days of re-illumination, T. weissflogii grew faster than of Rhodomonas sp.. The diatom seemed to benefit from better start conditions and would out-compete the cryptophyte during a spring bloom. Our results highlight that these algae groups have different strategies in dealing with darkness, which potentially endow diatoms with a competitive advantage in deep mixed waters and in the season of early spring. 相似文献
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Bettina Schmidt Thomas Tradler Jens-U. Rahfeld Birgit Ludwig Bunty Jain Karlheinz Mann K. Peter Rücknagel Bernhard Janowski Angelika Schierhorn Gerhard Küllertz Jörg Hacker Gunter Fischer 《Molecular microbiology》1996,21(6):1147-1160
Legionella pneumophila is the causative agent of a severe form of pneumonia in humans (Legionnaires’disease). A major virulence factor, the Mip protein (FK506-binding protein, FKBP25mem), belongs to the enzyme family of peptidyl-prolyl cis/trans isomerases (PPIases). Here we show that L. pneumophila Philadelphia I possesses an additional cytoplasmic PPiase at a level of enzyme activity comparable to that of FKBP25mem. The N-terminal amino acid sequence of the purified protein was obtained by Edman degradation and showed that the protein is a member of the cyclophilin family of PPIases. The Icy gene (Legionella cycophn) was cloned and sequenced. It encodes a putative 164-amino-acid protein with a molecular mass of 17 968 Da called L. pneumophila cyclophilin 18 (L. p. Cyp18). Amino acid sequence comparison displays considerable similarity to the cytoplasmic and the periplasmic cyclophilins of Escherichia coll with 60.5% and 51.5% identity, respectively. The substrate specificity and inhibition by cyclosporin A revealed a pattern that is typically found for other bacterial cyclophilins. An L. pneumophila Cyp18 derivative with a 19-amino-acid polypeptide extension including a 6-histi-dine tag and an enterokinase cleavage site exhibits 相似文献
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Thorsten Klampfl Jelena D. Milosevic Ana Puda Andreas Sch?negger Klaudia Bagienski Tiina Berg Ashot S. Harutyunyan Bettina Gisslinger Elisa Rumi Luca Malcovati Daniela Pietra Chiara Elena Matteo Giovanni Della Porta Lisa Pieri Paola Guglielmelli Christoph Bock Michael Doubek Dana Dvorakova Nada Suvajdzic Dragica Tomin Natasa Tosic Zdenek Racil Michael Steurer Sonja Pavlovic Alessandro M. Vannucchi Mario Cazzola Heinz Gisslinger Robert Kralovics 《PloS one》2013,8(10)
Exome sequencing of primary tumors identifies complex somatic mutation patterns. Assignment of relevance of individual somatic mutations is difficult and poses the next challenge for interpretation of next generation sequencing data. Here we present an approach how exome sequencing in combination with SNP microarray data may identify targets of chromosomal aberrations in myeloid malignancies. The rationale of this approach is that hotspots of chromosomal aberrations might also harbor point mutations in the target genes of deletions, gains or uniparental disomies (UPDs). Chromosome 11 is a frequent target of lesions in myeloid malignancies. Therefore, we studied chromosome 11 in a total of 813 samples from 773 individual patients with different myeloid malignancies by SNP microarrays and complemented the data with exome sequencing in selected cases exhibiting chromosome 11 defects. We found gains, losses and UPDs of chromosome 11 in 52 of the 813 samples (6.4%). Chromosome 11q UPDs frequently associated with mutations of CBL. In one patient the 11qUPD amplified somatic mutations in both CBL and the DNA repair gene DDB1. A duplication within MLL exon 3 was detected in another patient with 11qUPD. We identified several common deleted regions (CDR) on chromosome 11. One of the CDRs associated with de novo acute myeloid leukemia (P=0.013). One patient with a deletion at the LMO2 locus harbored an additional point mutation on the other allele indicating that LMO2 might be a tumor suppressor frequently targeted by 11p deletions. Our chromosome-centered analysis indicates that chromosome 11 contains a number of tumor suppressor genes and that the role of this chromosome in myeloid malignancies is more complex than previously recognized. 相似文献
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Marlene Fischer Anelia Dietmann Ronny Beer Gregor Broessner Raimund Helbok Bettina Pfausler Erich Schmutzhard Peter Lackner 《PloS one》2013,8(3)