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81.
Yu Y Harris RI Yang JL Anderson HC Walsh WR 《Journal of biomedical materials research. Part A》2004,70(1):122-128
Differential expression of multiple osteogenic factors may be responsible for the different osteoinductivity of osteosarcoma cell lines. We compared in vivo osteoinductivity of human osteosarcoma cell lines (Saos-2 vs. U-2 OS) in nude mice, and their in vitro expression of various osteogenic factors of protein level by quantitative immunocytochemistry and mRNA level by RT-PCR and/or in situ hybridization. Saos-2 cells, but not U-2 OS, were osteoinductive in vivo. Significantly higher expression (independent t-test, all p < 0.005) of osteogenic factors were observed in Saos-2 cells compared with U-2 OS, which included bone morphogenetic proteins (particularly BMPs-2, 3, 4, and 7), transforming growth factor-beta (TGF-beta), BMP receptor (BMPR)-1A, receptor-regulated Smads (R-Smads), Smads 1, 2, and 5, and common-mediator Smad (Co-Smad), Smad 4. In contrast, U-2 OS cells expressed higher levels of inhibitory Smad 6 (I-Smad) protein than Saos-2 cells (p < 0.001). These results suggest that a combination of osteogenic factors (BMPs, TGF-beta, BMPRs, and R/Co-Smads) against I-Smad may play important roles in the Saos-2 cell osteoinductivity. This may have a clinical implication in selecting key osteogenic factors for combined therapy for bone defect diseases. The characterized cell lines can be used as positive and negative controls for the assessments of both in vitro and in vivo bone formation capabilities of designed tissues or biomaterials. 相似文献
82.
Systematic changes in gene expression in postmortem human brains associated with tissue pH and terminal medical conditions 总被引:8,自引:0,他引:8
83.
Tumor Necrosis Factor Alpha Enhances Antifungal Activities of Polymorphonuclear and Mononuclear Phagocytes against Aspergillus fumigatus 总被引:4,自引:0,他引:4 下载免费PDF全文
Emmanuel Roilides Anastasia Dimitriadou-Georgiadou Tin Sein Isaac Kadiltsoglou Thomas J. Walsh 《Infection and immunity》1998,66(12):5999-6003
Invasive aspergillosis is a serious complication in immunocompromised patients. The effects of recombinant human tumor necrosis factor alpha (TNF-α) on antifungal activities of human neutrophils (polymorphonuclear leukocytes [PMNs]), human monocytes (MNCs), and rabbit pulmonary alveolar macrophages (PAMs) against Aspergillus fumigatus were studied. The percentage of PMN-induced hyphal damage was increased after 30 min of incubation of PMNs with 0.1 ng of TNF-α per ml at 37°C (P = 0.043). At 0.1 to 10 ng/ml, TNF-α also increased superoxide anion (O2−) produced by PMNs in response to phorbol myristate acetate, N-formylmethionyl leucyl phenylalanine, and unopsonized hyphae (P < 0.01) but did not exert any effect on PMN phagocytosis of conidia in the presence of serum. By comparison, TNF-α induced only a slight increase in O2− production by MNCs in response to phorbol myristate acetate (P = 0.05) and no concomitant increase in the percentage of MNC-induced hyphal damage. Incubation of MNCs with TNF-α at 0.001 to 10 ng/ml for 2 days had no effect on phagocytosis or conidiocidal activity. By contrast, incubation of PAMs with TNF-α at 0.1 to 10 ng/ml for 2 days increased phagocytosis of conidia (P = 0.03). Thus, TNF-α augments the capacity of PMNs to damage Aspergillus hyphae, possibly through enhanced oxidative mechanisms, and increases PAM phagocytic activity against conidia. As such, TNF-α may have an important role in host defense against aspergillosis, and neutralization of its activity may be complicated by increased susceptibility to aspergillosis. 相似文献
84.
The onset response pattern displayed by octopus cells has been attributed to intrinsic membrane properties, low membrane impedance, and/or synaptic inputs. Although the importance of a low membrane impedance generally is acknowledged as an essential component, views differ on the role that ion channels play in producing the onset response. In this study, we use a computer model to investigate the contributions of ion channels to the responses of octopus cells. Simulations using current ramps indicate that, during the "ramp-up" stage, the membrane depolarizes, activating a low-threshold K(+) channel, K(LT), which increases membrane conductance and dynamically increases the current required to evoke an action potential. As a result, the model is sensitive to the rate that membrane potential changes when initiating an action potential. Results obtained when experimentally recorded spike trains of auditory-nerve fibers served as model inputs (simulating acoustic stimulation) demonstrate that a model with K(LT) conductance as the dominant conductance produces realistic onset response patterns. Systematically replacing the K(LT) conductance by a h-type conductance (which corresponds to a hyperpolarization-activated inward rectifier current, I(h)) or by a leakage conductance reduces the model's sensitivity to rate of change in membrane potential, and the model's response to "acoustic stimulation" becomes more chopper-like. Increasing the h-type conductance while maintaining a large K(LT) conductance causes an increase in threshold to both current steps and acoustic stimulation but does not significantly affect the model's sensitivity to rate of change in membrane potential and the onset response pattern under acoustic stimulation. These findings support the idea that K(LT), which is activated during depolarization, is the primary membrane conductance determining the response properties of octopus cells, and its dynamic role cannot be provided by a static membrane conductance. On the other hand, I(h), which is activated during hyperpolarization, does not play a large role in the basic onset response pattern but may regulate response threshold through its contribution to the membrane conductance. 相似文献
85.
DRAK2 is a member of the death-associated protein (DAP)-like family of serine/threonine kinases. Members of this family induce apoptosis in various cell types. DRAK2, in particular, is specifically expressed in T cells and B cells, and it is differentially regulated during T cell development. To determine whether DRAK2 regulates lymphocyte apoptosis, we produced Drak2(-/-) mice. Contrary to our expectations, Drak2(-/-) T cells did not demonstrate any defects in apoptosis or negative selection; however, T cells from Drak2(-/-) mice exhibited enhanced sensitivity to T cell receptor-mediated stimulation with a reduced requirement for costimulation. These results provide evidence that DRAK2 raises the threshold for T cell activation by negatively regulating signals through the TCR. In contrast to other models of T cell hypersensitivity, Drak2(-/-) mice were remarkably resistant to experimental autoimmune encephalomyelitis (EAE). These results expose a new pathway regulating T cell activation and highlight the intricacies of induced autoimmune disease. 相似文献
86.
IMPT1, an imprinted gene similar to polyspecific transporter and multi- drug resistance genes 总被引:5,自引:1,他引:5
Dao D; Frank D; Qian N; O'Keefe D; Vosatka RJ; Walsh CP; Tycko B 《Human molecular genetics》1998,7(4):597-608
Human chromosome 11p15.5 and distal mouse chromosome 7 include a
megabase-scale chromosomal domain with multiple genes subject to parental
imprinting. Here we describe mouse and human versions of a novel imprinted
gene, IMPT1 , which lies between IPL and p57 KIP2 and which encodes a
predicted multi-membrane-spanning protein similar to bacterial and
eukaryotic polyspecific metabolite transporter and multi- drug resistance
pumps. Mouse Impt1 and human IMPT1 mRNAs are highly expressed in tissues
with metabolite transport functions, including liver, kidney, intestine,
extra-embryonic membranes and placenta, and there is strongly preferential
expression of the maternal allele in various mouse tissues at fetal stages.
In post-natal tissues there is persistent expression, but the allelic bias
attenuates. An allelic expression bias is also observed in human fetal and
post-natal tissues, but there is significant interindividual variation and
rare somatic allele switching. The fact that Impt1 is relatively repressed
on the paternal allele, together with data from other imprinted genes,
allows a statistical conclusion that the primary effect of human chromosome
11p15.5/mouse distal chromosome 7 imprinting is domain-wide relative
repression of genes on the paternal homolog. Dosage regulation of the
metabolite transporter gene(s) by imprinting might regulate placental and
fetal growth.
相似文献
87.
Krushkal J; Xiong M; Ferrell R; Sing CF; Turner ST; Boerwinkle E 《Human molecular genetics》1998,7(9):1379-1383
Elevated blood pressure is an important risk factor for renal-, cerebro-
and cardiovascular diseases. We used an efficient discordant sib-pair
ascertainment scheme to investigate the impact of the distal end of the
long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing
genes for the alpha1B and beta2 adrenergic receptors and the dopamine
receptor type 1A on variation of systolic blood pressure in young
Caucasians. We measured eight highly polymorphic markers spanning this
positional candidate gene-rich region in 427 individuals from 55
three-generation pedigrees containing 69 discordant sibling pairs, and
calculated multipoint identity by descent (MIBD) probabilities. The results
of genetic linkage and association tests indicate that the region between
markers D5S2093 and D5S462 is significantly linked to one or more
polymorphic genes influencing interindividual variation in systolic blood
pressure levels. Since the alpha1B adrenergic receptor and dopamine
receptor type 1A genes are located close to these markers, these data
suggest that genetic variation in one or both of these G protein-coupled
receptors, which participate in the control of vascular tone, plays an
important role in influencing interindividual variation in systolic blood
pressure levels.
相似文献
88.
Trichosporon beigelii, an emerging pathogen resistant to amphotericin B. 总被引:12,自引:2,他引:12
T J Walsh G P Melcher M G Rinaldi J Lecciones D A McGough P Kelly J Lee D Callender M Rubin P A Pizzo 《Journal of clinical microbiology》1990,28(7):1616-1622
Trichosporon beigelii caused fatal disseminated infections that were resistant to amphotericin B in two granulocytopenic patients. In vitro susceptibility studies demonstrated that both index strains of T. beigelii were inhibited but not killed by amphotericin B at achievable concentrations in serum. The minimum lethal concentration for both isolates was greater than or equal to 18 micrograms/ml. Five of seven other isolates were found to have a similar pattern of amphotericin B resistance. The fact that the minimum lethal concentration of T. beigelii was many times greater than its MIC was consistent with a resistance pattern of tolerance. We concluded that T. beigelii may be resistant in vitro to amphotericin B and that this in vitro resistance was correlated with refractory, disseminated trichosporonosis in granulocytopenic patients. T. beigelii should be included in the expanding list of amphotericin B-resistant fungi. 相似文献
89.
Characterisation of a subtype of colorectal cancer combining features of the suppressor and mild mutator pathways 总被引:18,自引:0,他引:18 下载免费PDF全文
Jass JR Biden KG Cummings MC Simms LA Walsh M Schoch E Meltzer SJ Wright C Searle J Young J Leggett BA 《Journal of clinical pathology》1999,52(6):455-460
BACKGROUND: 10% of sporadic colorectal cancers are characterised by a low level of microsatellite instability (MSI-L). These are not thought to differ substantially from microsatelite-stable (MSS) cancers, but MSI-L and MSS cancers are distinguished clinicopathologically and in their spectrum of genetic alterations from cancers showing high level microsatellite instability (MSI-H). AIMS: To study the distribution of molecular alterations in a series of colorectal cancers stratified by DNA microsatellite instability. METHODS: A subset of an unselected series of colorectal cancers was grouped by the finding of DNA MSI at 0 loci (MSS) (n = 51), 1-2 loci (MSI-L) (n = 38) and 3-6 loci (MSI-H) (n = 25). The frequency of K-ras mutation, loss of heterozygosity (LOH) at 5q, 17p and 18q, and patterns of p53 and beta catenin immunohistochemistry was determined in the three groups. RESULTS: MSI-H cancers had a low frequency of K-ras mutation (7%), LOH on chromosomes 5q (0%), 17p (0%) and 18q (12.5%), and a normal pattern of immunostaining for p53 and beta catenin. MSI-L cancers differed from MSS cancers in terms of a higher frequency of K-ras mutation (54% v 27%) (p = 0.01) and lower frequency of 5q LOH (23% v 48%) (p = 0.047). Whereas aberrant beta catenin expression and 5q LOH were concordant (both present or both absent) in 57% of MSS cancers, concordance was observed in only 20% of MSI-L cancers (p = 0.01). CONCLUSIONS: MSI-L colorectal cancers are distinct from both MSI-H and MSS cancers. This subset combines features of the suppressor and mutator pathways, may be more dependent on K-ras than on the APC gene in the early stages of neoplastic evolution, and a proportion may be related histogenetically to the serrated (hyperplastic) polyp. 相似文献
90.
Four groups of adult rats, housed on a 12-12, light-dark cycle, were allowed access to a nutritionally complete diet and water. Three of these groups were also offered a 32% solution of sucrose. The sucrose was available for either the 24-hour period, the 12 hours of light or the 12 hours of dark. Access to sucrose led to overeating and excessive weight gain. These effects were more pronounced when the sucrose was available for the 24-hour period or during the dark. Limited access to sucrose produced a reversal of the rat's usual circadian pattern of feeding when the sucrose was available during the light and increased the rat's nocturnal hyperphagia when it was available during the dark. Sucrose intake and the proportion of calories taken from sucrose were higher in the 24-hour access group and the dark access group than the light access group. Access to sucrose did not induce a pattern of dietary selection that compromised growth or health. It appears that access to a palatable carbohydrate solution can lead to overeating and major changes in the circadian organization of feeding behavior. These data emphasize the potent role that external factors can play in the control of ingestive behavior. 相似文献