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41.
Background: Proteins generally enter or exit the nucleus as cargo of one of a small family of import and export receptors. These receptors bear distant homology to importin β, a subunit of the receptor for proteins with classical nuclear localisation sequences (NLSs). To understand the mechanism of nuclear transport, the next question involves identifying the nuclear pore proteins that interact with the different transport receptors as they dock at the pore and translocate through it.Results: Two pathways of nuclear import were found to intersect at a single nucleoporin, Nup153, localized on the intranuclear side of the nuclear pore. Nup153 contains separate binding sites for importin α/β, which mediates classical NLS import, and for transportin, which mediates import of different nuclear proteins. Strikingly, a Nup153 fragment containing the importin β binding site acted as a dominant-negative inhibitor of NLS import, with no effect on transportin-mediated import. Conversely, a Nup153 fragment containing the transportin binding site acted as a strong dominant-negative inhibitor of transportin import, with no effect on classical NLS import. The interaction of transportin with Nup153 could be disrupted by a non-hydrolyzable form of GTP or by a GTPase-deficient mutant of Ran, and was not observed if transportin carried cargo. Neither Nup153 fragment affected binding of the export receptor Crm1 at the nuclear rim.Conclusions: Two nuclear import pathways, mediated by importin β and transportin, converge on a single nucleoporin, Nup153. Dominant-negative fragments of Nup153 can now be used to distinguish different nuclear import pathways and, potentially, to dissect nuclear export. 相似文献
42.
Experimental Trichinella infection in seals 总被引:2,自引:0,他引:2
Kapel CM Measures L Møller LN Forbes L Gajadhar A 《International journal for parasitology》2003,33(13):1463-1470
The susceptibility of seals to infection with Trichinella nativa and the cold tolerant characteristics of muscle larvae in seal meat were evaluated. Two grey seals, Halichoerus grypus, were inoculated with 5000 (100 larvae/kg) T. nativa larvae and two grey seals with 50000 (1000 larvae/kg). One seal from each dose group and two control seals were killed at 5 and 10 weeks post-inoculation (p.i.). At 5 weeks p.i., infection was established in both low and high dose seals with mean larval densities of 68 and 472 larvae per gram (lpg), respectively, using eight different muscles for analyses. At 10 weeks p.i., mean larval densities were 531 and 2649 lpg, respectively, suggesting an extended persistence of intestinal worms. In seals with high larval density infections, the distribution of larvae in various muscles was uniform, but in one seal with a low larval density infection, predilection sites of larvae included muscle groups with a relative high blood flow, i.e. diaphragm, intercostal and rear flipper muscles. Trichinella-specific antibody levels, as measured by ELISA, increased during the 10 week experimental period. Infected seal muscle was stored at 5, -5 and -18 degrees C for 1, 4 and 8 weeks. Muscle larvae released from stored seal muscle by artificial digestion were inoculated into mice to assess viability and infectivity. Larvae from seal muscle 10 weeks p.i. tolerated -18 degrees C for 8 weeks but larvae from seal muscle 5 weeks p.i. tolerated only 1 week at -18 degrees C, supporting the hypothesis that freeze tolerance increases with the age of the host-parasite tissue complex. The expressed susceptibility to infection, extended production of larvae, antibody response and freeze tolerance of T. nativa in seals are new findings from the first experimental Trichinella infection in any marine mammal and suggest that pinnipeds (phocids, otariiids or walrus) may acquire Trichinella infection by scavenging even small amounts of infected tissue left by hunters or predators. 相似文献
43.
Control of expression of the I factor, a LINE-like transposable element in Drosophila melanogaster. 下载免费PDF全文
I factors are LINE-like transposable elements in the genome of Drosophila melanogaster. They normally transpose infrequently but are activated in the germline of female progeny of crosses between males of a strain that contains complete elements, an I or inducer strain and females of a strain that does not, an R or reactive strain. This causes a phenomenon known as I-R hybrid dysgenesis. We have previously shown that the I factor promoter lies between nucleotides 1 and 30. Here we demonstrate that expression of this promoter is regulated by nucleotides 41-186 of the I factor. This sequence can act as an enhancer as it stimulates expression of the hsp7O promoter in ovaries in the absence of heat-shock. Within this region there is a site that is required for promoter activity and that is recognized by a sequence-specific binding protein. We propose that this protein contributes to the enhancer activity of nucleotides 41-186 and that reduced I factor expression in inducer strains is due to titration of this protein or others that interact with it. 相似文献
44.
Emma?M.M. Burkitt?Wright Helen?L. Spencer Sarah?B. Daly Forbes?D.C. Manson Leo?A.H. Zeef Jill Urquhart Nicoletta Zoppi Richard Bonshek Ioannis Tosounidis Meyyammai Mohan Colm Madden Annabel Dodds Kate?E. Chandler Siddharth Banka Leon Au Jill Clayton-Smith Naz Khan Leslie?G. Biesecker Meredith Wilson Marianne Rohrbach Marina Colombi Cecilia Giunta Graeme?C.M. Black 《American journal of human genetics》2011,89(2):346
45.
Population density and infection with parasites often are important factors affecting the growth and development of individuals.
How these factors co-occur and interact in nature should have important consequences for individual fitness and higher-order
phenomena, such as population dynamics of hosts and their interactions with other species. However, few studies have examined
the joint effects of density and parasitism on host growth and development. We examined the co-influences of rearing density
and parasitism, by the trematode Echinostoma trivolvis, on the growth and development of larval frogs, Rana (=Lithobates) pipiens. We also examined the potential role of parasite-mediated intraspecific competition by observing how unparasitized individuals
performed when housed with other unparasitized tadpoles, versus housing with a combination of unparasitized and parasitized
hosts. Mean mass and mean developmental stage were reduced under high rearing densities. The presence of parasitized conspecifics
had no significant effect, but there was a significant interaction of density and parasitism presence on host mass, due to
the fact that parasitized conspecifics grew poorly at high densities. Unparasitized individuals reared with parasitized and
unparasitized conspecifics fared no better than unparasitized individuals reared only with one another. This result indicates
that infected hosts compete as much as uninfected hosts for resources, even though infected individuals have reduced mass
under high-density conditions. Resource acquisition and resource allocation are different processes, and parasitism, if it
only affects the latter, might not have a discernible impact on competitive interactions. 相似文献
46.
Small KM Brown KM Forbes SL Liggett SB 《The Journal of biological chemistry》2001,276(34):31596-31601
Depressed G-protein-coupled receptor (GPCR) signaling has been implicated as a component of the pathophysiology of a number of complex diseases including heart failure and asthma, and augmentation or restoration of signaling by various means has been shown to improve organ function. Because some properties of native GPCRs are disadvantageous for ectopic therapeutic expression, we utilized the beta(2)-adrenergic receptor (beta(2)AR) as a scaffold to construct a highly modified therapeutic receptor-effector complex (TREC) suitable for gene therapy. Altogether, 19 modifications were made to the receptor. The ligand-binding site was re-engineered in TM-3 so that a beta-hydroxylmethyl side chain acts as a proton donor for the binding of a novel ligand. In addition, sites critical for agonist-promoted down-regulation in the amino terminus and for phosphorylation by GPCR kinases, and protein kinases A and C, in the third intracellular loop and the carboxyl terminus of the receptor were altered. These modifications of the receptor resulted in depressed agonist-stimulated adenylyl cyclase activity (26.8 +/- 2.1 versus 41.4 +/- 8 pmol/min/mg for wild-type beta(2)AR). This was fully restored by fusing the carboxyl terminus of the modified receptor to G alpha(s) (43.3 +/- 2.7 pmol/min/mg). The fully modified fused receptor was not activated by beta-agonists but rather by a nonbiogenic amine agonist that itself failed to activate the wild-type beta(2)AR. This two-way selectivity thus provides targeted activation based on physiologic status. Furthermore, the TREC did not display tachyphylaxis to prolonged agonist exposure (desensitization was 1 +/- 5% versus 55 +/- 4% for wild-type beta(2)AR). Thus, despite extensive alterations in regions of conformational lability, the beta(2)AR can be tailored to have optimal signaling characteristics for gene therapy. As a general paradigm, TRECs for enhancement of other G-protein signaling appear to be feasible for modification of other pathologic states. 相似文献
47.
Four juvenile male wolves (Canis lupus) each received an oral dose of 1.6-1.7 x 10(12) colony-forming units of Brucella abortus biovar 1 isolated from a bison (Bison bison) in Wood Buffalo National Park (Canada), and two others served as negative controls. Infected wolves did not show clinical signs of disease but did develop high Brucella antibody titers. Small numbers of B. abortus were excreted sporadically in feces until day 50 postinoculation (PI). Very small numbers of the bacterium were isolated from urine of only one wolf late on the same day that it was infected, and very small numbers of colonies of B. abortus were obtained from buccal swabs of three wolves for up to 48 hr PI. Two infected wolves euthanized 6 mo after the start of the experiment had no lesions, and colonies of B. abortus were isolated from thymus and most major lymph nodes. The other two infected wolves euthanized 12 mo after the start of the experiment had no lesions, and smaller numbers of brucellae were recovered from fewer lymph nodes compared with the wolves killed 6 mo earlier. The sporadic excretion of very small numbers of brucellae by the wolves was insignificant when compared with the infective dose for cattle. Brucella abortus, brucellosis, Canis lupus, pathogenesis, serology, wolf. 相似文献
48.
The purpose of this study was to investigate enophthalmos by measuring the volume of various orbital structures using off-line computer techniques on images generated by a CT scanner. Eleven patients with enophthalmos had CT scans of the orbits consisting of 30 to 40 adjacent 1.5-mm slices. The data from the scans were analyzed on a Nova 830 stand-alone computer system using software programs that allowed measurement of total bony orbital volume, total soft-tissue volume, globe volume, orbital fat volume, neuromuscular tissue volume, and apex-to-globe distance in the horizontal plane. These data were analyzed comparing the volumes in the normal eye with the volumes in the enophthalmic eye in each patient. The analysis demonstrated a statistically significant increase in bony orbital volume in the enophthalmic eye, but the total soft-tissue volume, fat volume, neuromuscular tissue volume, and globe volume were the same as in the normal eye. The apex-to-globe distance, a measure of the degree of enophthalmos, was less in the enophthalmic eye than in the normal eye. These results suggest that in the majority of patients, the cause of posttraumatic enophthalmos is increased bony orbital volume rather than by soft-tissue loss or fat necrosis. (Several patients showed no volume discrepancies, and it is likely that cicatricial contracture is responsible for the enophthalmos in these cases.) This study suggests that the objective of surgery for correction of enophthalmos in patients with a volume discrepancy should be to decrease the volume of the bony orbit and to increase the anterior projection of the globe. 相似文献
49.
50.
We found evidence that a nematode (Skrjabinoclava morrisoni)
adaptivelymanipulates the behavior of its intermediate host (the amphipod
Corophiumvolutator) to increase its likelihood of transmission to
itsfinal host (the semipalmated sandpiper, Calidris pusilla). We
foundthat male and female amphipods parasitized by nematodes increasedtheir
surface activity in the field during daytime, but notduring nighttime hours.
Increased surface activity is knownto increase susceptibility of amphipods to
predation by sandpipersduring the day, but not at night, when sandpipers do
not feedvisually. Also, as predicted by the manipulation hypothesis,only
late-stage (infective) larvae of nematodes were associatedwith behavioral
changes of amphipods. We found no evidence thatparasites were associated with
other amphipod behaviors in thelaboratory, such as trail complexity, distance
traveled, orburrow-probing activity of crawling males as would be expectedif
parasitized hosts altered their own behavior. Survivorshipof amphipods was
also unaffected by parasitism, which may favorparasite transmission. Thus,
behavioral changes of parasitizedhosts were simple, and their expression was
context-dependentand related to likelihood of predation. We argue that
maturationtimes of nematodes in relation to migration schedules of sandpipers
providea narrow window of opportunity and may explain why nematodes
manipulateamphipod behavior. 相似文献