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61.
Comparative analysis of diffusive and stress induced nutrient transport efficiency in the lacunar-canalicular system of osteons 总被引:3,自引:0,他引:3
Marker migration experiments suggest that cyclic mechanical loading of cortical bone in vivo increases marker penetration into bone. Is this a result of stress induced fluid flow or of stress stimulation of active transport processes? Active lacunar-canalicular transport of nutrients was suggested by Ham in 1979 on the basis of the presence of actin filaments in osteocyte processes and their suspected role in cell motility. In addition, Tanaka in 1984 observed active transport of microperoxidase in bone and Tanaka-Kamioka et al. in 1998 observed experimentally that osteocyte processes are able to actively change their form. In this study we performed parametric and comparative analyses of the transport efficiencies of diffusion and stress generated fluid flow of (glucose) nutrients in lacunar-canalicular systems in cortical bone. The result obtained is that neither diffusion nor stress induced fluid flow is capable of sustaining osteocyte viability. It is possible that cyclic stress stimulates an active nutrient transport mechanism to supplement stress flows. 相似文献
62.
Yakovenko O Blyakhman F Pollack GH 《American journal of physiology. Cell physiology》2002,283(3):C735-C742
In attempting to deduce the size of theelementary molecular translation step, recent experiments using singlemyosin molecules translating over actin filaments have shown aconsistent step size of 5.4 nm (10, 21). We have carriedout parallel measurements on single myofibrils from rabbit cardiacmuscle and bumblebee flight muscle. Activated specimens were releasedor stretched with a motor-imposed ramp, and the time course of lengthof individual sarcomeres was measured by projecting the image of thestriations onto a linear photodiode array and tracking the spacingbetween A-band centroids. We confirmed the 5.4-nm step. Withsubnanometer precision, however, we find that this value is two timesthat of a more fundamental step size of 2.7 nm. Step sizes were always integer multiples of 2.7 nm, whether the length change was positive ornegative. This value is equal to the linear repeat of actin monomersalong the thin filament, a result that ties dynamic events to molecularstructure and places narrow constraints on any proposed molecular mechanism. 相似文献
63.
On the origin of modular variation 总被引:10,自引:1,他引:9
Lipson H Pollack JB Suh NP 《Evolution; international journal of organic evolution》2002,56(8):1549-1556
We study the dynamics of modularization in a minimal substrate. A module is a functional unit relatively separable from its surrounding structure. Although it is known that modularity is useful both for robustness and for evolvability (Wagner 1996), there is no quantitative model describing how such modularity might originally emerge. Here we suggest, using simple computer simulations, that modularity arises spontaneously in evolutionary systems in response to variation, and that the amount of modular separation is logarithmically proportional to the rate of variation. Consequently, we predict that modular architectures would appear in correlation with high environmental change rates. Because this quantitative model does not require any special substrate to occur, it may also shed light on the origin of modular variation in nature. This observed relationship also indicates that modular design is a generic phenomenon that might be applicable to other fields, such as engineering: Engineering design methods based on evolutionary simulation would benefit from evolving to variable, rather than stationary, fitness criteria, as a weak and problem-independent method for inducing modularity. 相似文献
64.
We present the elements of a mathematical computational model that reflects the experimental finding that the time-scale of a neuron is not fixed; but rather varies with the history of its stimulus. Unlike most physiological models, there are no pre-determined rates associated with transitions between states of the system nor are there pre-determined constants associated with adaptation rates; instead, the model is a kind of "modulating automata" where the rates emerge from the history of the system itself. We focus in this paper on the temporal dynamics of a neuron and show how a simple internal structure will give rise to complex temporal behavior. The internal structure modeled here is an abstraction of a reasonably well-understood physiological structure. We also suggest that this behavior can be used to transform a "rate" code into a "temporal one". 相似文献
65.
Physical mapping of genes in somatic cell radiation hybrids by comparative genomic hybridization to cDNA microarrays 总被引:1,自引:0,他引:1
Lin JY Pollack JR Chou FL Rees CA Christian AT Bedford JS Brown PO Ginsberg MH 《Genome biology》2002,3(6):research0026.1-research00267
Background
Somatic cell mutants can be informative in the analysis of a wide variety of cellular processes. The use of map-based positional cloning strategies in somatic cell hybrids to analyze genes responsible for recessive mutant phenotypes is often tedious, however, and remains a major obstacle in somatic cell genetics. To fulfill the need for more efficient gene mapping in somatic cell mutants, we have developed a new DNA microarray comparative genomic hybridization (array-CGH) method that can rapidly and efficiently map the physical location of genes complementing somatic cell mutants to a small candidate genomic region. Here we report experiments that establish the validity and efficacy of the methodology. 相似文献66.
Reactive oxygen species and induction of lignin peroxidase in Phanerochaete chrysosporium 总被引:2,自引:0,他引:2
Belinky PA Flikshtein N Lechenko S Gepstein S Dosoretz CG 《Applied and environmental microbiology》2003,69(11):6500-6506
We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O(2)) of Phanerochaete chrysosporium by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O(2) gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O(2) (oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O(2) concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O(2) is at least partially mediated by the intracellular ROS. 相似文献
67.
BACKGROUND: Estimating the duration of S phase (T(S) ) and the potential doubling time (T(pot) ) from a single time measurement of the movement of cells using bivariate cytometry is common. However, these estimates require an assumption of the duration of G2 + M (T(G2+M) ). Inspection of the measured dynamic quantities, relative movement [RM(t)], fractions of labeled divided and undivided cells (f(lu)(t) and f(ld)(t)) suggests that T(G2+M), T(S), and T(pot) can be determined simultaneously. METHODS: An equation connecting the growth of the cell population, time, and the dynamic quantities was determined. The equation cannot be solved analytically, but accurate approximations can be used to find T(pot). From this result, the value of T(G2+M) can be determined from f(ld)(t), and T(S) can be determined from RM(t). RESULTS: Kinetic parameters obtained from single time estimates using the new method compared to those obtained from the analysis of multiple time-point measurements of MCa-K and MCa-4 murine tumors are shown to be in close agreement. Moreover, estimates of T(G2+M) in MCa-4 tumors, treated with paclitaxel, provide extra information on the changes in T(G2+M). When applied to the rat R3327-G prostate tumor model following androgen ablation, a correlation analysis of the T(pot) values obtained by the new and previous single time-point methods demonstrates that the rank order from shortest to longest T(pot) values are largely preserved. CONCLUSIONS: The new procedure makes direct estimation of T(G2+M) possible from single time-dynamic measurements. The results from previous studies on T(S) and T(pot) are largely unchanged, but extra information is now available. 相似文献
68.
Induction of antitumor immunity by indomethacin 总被引:4,自引:0,他引:4
Morecki S Yacovlev E Gelfand Y Trembovler V Shohami E Slavin S 《Cancer immunology, immunotherapy : CII》2000,48(11):613-620
Irradiated tumor cells given, together with indomethacin, to syngeneic mice induced an antitumor response and conferred protection
against a challenge of a lethal dose of murine mammary (4T1) and lung (3LL) carcinoma cells. Continuous administration of
indomethacin was crucial throughout the entire period of immunization and challenge, as no protection was achieved when the
drug was given during only one of these procedures. Antitumor immunity was long-lasting and, when tested in the 4T1 model,
48% of mice were resistant to a second challenge of lethal tumor cells. Tumor-free immune mice that were given indomethacin
for more than 300 days remained healthy with normal white blood cell counts and normal spleen size. Cells isolated from immune
mice were able to kill tumor cells in culture after in vitro activation by interleukin-2, in a manner similar to cells from
naive normal control mice. In addition, the mitogenic response of their T cells was as high as that of the control naive mice.
While indomethacin was able to induce antitumor immunity to 4T1 and 3LL murine carcinoma cells, both of which contain a high
concentration of endogenic prostaglandin E2 (PGE2), no such immunity was achieved to murine tumor cells with a low concentration of endogenic PGE2. These results suggest
a correlation between PGE2 concentration and the ability of indomethacin to induce antitumor immunity. We therefore suggest
that an immunotherapy protocol with long-term dispensation of a tolerable dose of an immunomodulator, given together with
irradiated autologous tumor cells, may stimulate antitumor responses to tumors containing high concentrations of endogenic
PGE2.
Received: 12 August 1999 / Accepted: 21 September 1999 相似文献
69.
Induction of determinant spreading and of Th1 responses by in vitro stimulation with HER-2 peptides 总被引:2,自引:2,他引:0
Anderson BW Kudelka AP Honda T Pollack MS Gershenson DM Gillogly MA Murray JL Ioannides CG 《Cancer immunology, immunotherapy : CII》2000,49(9):459-468
Immunization with tumor antigens induces cellular and humoral immune responses. These responses by T cells are specific for
defined epitopes (determinants) in the molecule of the immunizing tumor antigen. Extension of such responses to self-antigens
requires induction of autoimmunity to the tumor. As with systems of autoimmune disease, expression of T cell autoimmunity
is charaterized by diversification of responses from the inducer determinant to other responder (cryptic) determinants. Since
similar strategies may be useful for therapy of human cancers, we investigated whether the induction of response to a HER-2
peptide F7 (776–789) induces enhanced reactivity of other HER-2 peptides. We found that stimulation with F7 can expand a response
to another epitope F13 (884–899) in both an ovarian cancer patient with progressive disease and a healthy donor who shared
HLA-DR11. This response was characterized mainly by increased interferon γ secretion, and proliferation, but was not observed
with another donor who shared HLA-DR14 and HLA-DQ5 with the patient. Since repeated vaccination with the same epitope may
lead to a decline of primary cell reactivity caused by apoptosis spreading the response to other epitopes, the tumor antigen
may provide an approach for maintaining an inflammatory Th1 response during cancer vaccination.
Received: 10 April 2000 / Accepted: 12 July 2000 相似文献
70.
We investigated the effect of newborn bovine serum on the intracellular calcium [Ca2+]i response of primary cultured bone cells stimulated by fluid flow. As it has been previously established that these cells exhibit [Ca2+]i responses to fluid flow shear stress in saline media without growth factors or other chemically stimulatory factors, we hypothesized that the addition of serum to the flow medium would enhance the mechanosensitivity of the cells. We examined the effect of a short-term (10–15 min) exposure of the cells to 2 and 10% serum prior to flow stimulation (pretreated) compared to not exposing the cells prior to flow stimulation (unpretreated). The cells were subjected to a well-defined, 90-s flow stimulus with shear stress levels ranging from 0.02 to 3.5 Pa in a laminar flow chamber using a saline medium supplemented with 2 or 10% serum. For pretreatment, the serum concentration was the same from pre-flow to flow exposure. We observed a differential effect in the magnitude of the peak [Ca2+]i response modulated by the concentration of serum in the pre-flow medium. Additionally, ATP-supplemented flow was examined as a comparison to the serum-supplemented flow and exhibited a similar trend in the peak [Ca2+]i flow response that was dependent on ATP concentration and pre-flow exposure conditions. These findings demonstrate that under the conditions of this study, chemical agonist exposure can modulate the [Ca2+]i response in bone cells subjected to fluid flow-induced shear stress. 相似文献