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101.
The U11/U12 snRNP 65K protein acts as a molecular bridge, binding the U12 snRNA and U11-59K protein 下载免费PDF全文
U11 and U12 interact cooperatively with the 5' splice site and branch site of pre-mRNA as a stable preformed di-snRNP complex, thereby bridging the 5' and 3' ends of the intron within the U12-dependent prespliceosome. To identify proteins contributing to di-snRNP formation and intron bridging, we investigated protein-protein and protein-RNA interactions between components of the U11/U12 snRNP. We demonstrate that the U11/U12-65K protein possesses dual binding activity, interacting directly with U12 snRNA via its C-terminal RRM and the U11-associated 59K protein via its N-terminal half. We provide evidence that, in contrast to the previously published U12 snRNA secondary structure model, the 3' half of U12 forms an extended stem-loop with a highly conserved seven-nucleotide loop and that the latter serves as the 65K binding site. Addition of an oligonucleotide comprising the 65K binding site to an in vitro splicing reaction inhibited U12-dependent, but not U2-dependent, pre-mRNA splicing. Taken together, these data suggest that U11/U12-65K and U11-59K contribute to di-snRNP formation and intron bridging in the minor prespliceosome. 相似文献
102.
Growth of high quality crystals is often the most difficult step in the determination of protein structures by X-ray diffraction. Automation can improve the success of this process both by reducing the amount of protein required for each screen and by relieving the tedium of setting up crystallization experiments by hand. We have been using an automated system for the design and execution of hanging drop crystallization experiments for the last two years. The system includes robots for the preparation of solutions, setup of hanging drops, and automated imaging, as well as a new software package (RoCKS) for managing all phases of the crystallization process. Here, we review the fundamentals of automated protein crystallization and present results from our comparisons of various approaches to screening. 相似文献
103.
Protein composition of human mRNPs spliced in vitro and differential requirements for mRNP protein recruitment 总被引:4,自引:2,他引:4 下载免费PDF全文
The deposition of proteins onto newly spliced mRNAs has far reaching consequences for their subsequent metabolism. We affinity-purified spliced human mRNPs under physiological conditions from HeLa nuclear extract and present the first comprehensive inventory of their protein composition as determined by mass spectrometry. Several proteins previously not known to be mRNP-associated were detected, including the DEAD-box helicases DDX3, DDX5, and DDX9, and the ELG, hNHN1, BCLAF1, and TRAP150 proteins. The association of some of the newly identified mRNP proteins was shown to be splicing-dependent, but not to require EJC formation. Initial recruitment of EJC proteins to the spliceosome did not require an EJC binding platform at the -20/24 region of the 5' exon. Finally, while recruitment of EJC proteins and stable EJC formation were not dependent on the cap binding complex, several of the newly identified mRNP proteins required the latter for their association with mRNPs. These results provide novel insights into the composition of spliced mRNPs and the requirements for the association of mRNP proteins with the newly spliced mRNA. 相似文献
104.
Intraflock variation in the speed of escape-flight response on attack by an avian predator 总被引:5,自引:2,他引:5
The benefits of flocking to prey species, whether through collective
vigilance,dilution of risk, or predator confusion, depend on flock members
respondingin a coordinated way to attack. We videotaped sparrowhawks
attackingredshank flocks to determine if there were differences in thetiming
of escape flights between flock members and the factorsthat might affect any
differences. Sparrowhawks are surpriseshort-chase predators, so variation in
the time taken to takeflight on attack is likely to be a good index of
predation risk.Most birds in a flock flew within 0.25 s of the first bird
flying,and all birds were flying within 0.7 s. Redshanks that werevigilant,
that were closest to the approaching raptor, and thatwere close to their
neighbors took flight earliest within aflock. Birds in larger flocks took
longer, on average, to takeflight, measured from the time that the first bird
in the flockflew. Most birds took flight immediately after near neighbors
tookoff, but later flying birds were more likely to fly immediatelyafter
more distant neighbors took flight. This result, alongwith the result that
increased nearest neighbor distance increasedflight delay, suggests that most
redshanks flew in responseto conspecifics flying. The results strongly
suggest that thereis significant individual variation in predation risk
withinflocks so that individuals within a flock will vary in benefitsthat
they gain from flocking. 相似文献
105.
Andreas Mund Tobias Schubert Hannah Staege Sarah Kinkley Kerstin Reumann Malte Kriegs Lauriane Fritsch Valentine Battisti Slimane Ait-Si-Ali Anne-Sophie Hoffbeck Evi Soutoglou Hans Will 《Nucleic acids research》2012,40(22):11363-11379
Survival time-associated plant homeodomain (PHD) finger protein in Ovarian Cancer 1 (SPOC1, also known as PHF13) is known to modulate chromatin structure and is essential for testicular stem-cell differentiation. Here we show that SPOC1 is recruited to DNA double-strand breaks (DSBs) in an ATM-dependent manner. Moreover, SPOC1 localizes at endogenous repair foci, including OPT domains and accumulates at large DSB repair foci characteristic for delayed repair at heterochromatic sites. SPOC1 depletion enhances the kinetics of ionizing radiation-induced foci (IRIF) formation after γ-irradiation (γ-IR), non-homologous end-joining (NHEJ) repair activity, and cellular radioresistance, but impairs homologous recombination (HR) repair. Conversely, SPOC1 overexpression delays IRIF formation and γH2AX expansion, reduces NHEJ repair activity and enhances cellular radiosensitivity. SPOC1 mediates dose-dependent changes in chromatin association of DNA compaction factors KAP-1, HP1-α and H3K9 methyltransferases (KMT) GLP, G9A and SETDB1. In addition, SPOC1 interacts with KAP-1 and H3K9 KMTs, inhibits KAP-1 phosphorylation and enhances H3K9 trimethylation. These findings provide the first evidence for a function of SPOC1 in DNA damage response (DDR) and repair. SPOC1 acts as a modulator of repair kinetics and choice of pathways. This involves its dose-dependent effects on DNA damage sensors, repair mediators and key regulators of chromatin structure. 相似文献
106.
Joy Gardner Penny A. Rudd Natalie A. Prow Essia Belarbi Pierre Roques Thibaut Larcher Lionel Gresh Angel Balmaseda Eva Harris Wayne A. Schroder Andreas Suhrbier 《PloS one》2015,10(10)
Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities. 相似文献
107.
Osmoregulatory effects of hypophysectomy and homologous prolactin replacement in hybrid striped bass
Jackson LF McCormick SD Madsen SS Swanson P Sullivan CV 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》2005,140(2):211-218
The effects of ovine prolactin (oPRL) and striped bass prolactin (sbPRL; Morone saxatilis) on plasma osmolality, electrolyte balance, and gill Na(+),K(+)-ATPase activity were investigated in hypophysectomized (Hx), freshwater (FW)-acclimated, hybrid striped bass (M. saxatilisxMorone chrysops). They were kept in dilute (isoosmotic) seawater for about 10 days after surgery. Seven days after transfer to FW, Hx fish had lower plasma osmolality and lower levels of Na(+), Cl(-), and Ca(2+) than sham-operated and intact fish. Fish were injected four times with oPRL (1, 5, or 20 microg/g body mass), sbPRL (10 or 100 ng/g), or hormone vehicle (0.9% NaCl) at 48-h intervals (days 0, 2, 4, and 6) in FW and then sampled for blood plasma 24 h after the fourth injection (day 7). In Hx fish, oPRL (5 and 20 microg/g) and sbPRL (10 and 100 ng/g) were effective in maintaining plasma osmolality and levels of Na(+), Cl(-), and Ca(2+) above values seen in saline-injected controls. Hypophysectomy did not affect branchial Na(+),K(+)-ATPase activity, but enzyme activity was significantly reduced in Hx fish receiving oPRL (20 mug/g) or sbPRL (10 or 100 ng/g). These results indicate that PRL acts to maintain plasma osmotic and ionic balance in FW-adapted hybrid striped bass, and that this may involve downregulation of branchial Na(+),K(+)-ATPase activity. 相似文献
108.
Summary Cultures generated from tissues consisting of multiple types of cells are often heterogeneous. Unless the cell type of interest
has or can be given some selective growth advantage it may be overgrown by other cells. While developing techniques for the
tissue culture of microvascular endothelial cells we evaluated an electrosurgical generator (diathermy) to selectively kill
nonendothelail cells. Primary cell cultures were observed at ×100 magnification under phase contrast microscopy and a needle
electrode apposed to the cell to be destroyed. A return electrode was constructed by placing a sterile clip in contact with
the culture medium. The diathermy power setting controlled the area of lysis. Use of this technique allowed weeding of unwanted
cells without damage to endothelial cells, which were able to grow to confluence in pure culture.
Dr. Marks receives a Medical Postgraduate Research Scholarship from the National Health and Medical Research Council of Australia.
Financial support was received from the Leo Leukaemia and Cancer Research Trust and the Scleroderma Association of New South
Wales. 相似文献
109.
110.
Dennis?M?Maddox Anna?Manlapat Penny?Roon Puttur?Prasad Vadivel?Ganapathy Sylvia?B?SmithEmail author 《BMC developmental biology》2003,3(1):6