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101.
Control of B cell production by the adaptor protein lnk. Definition Of a conserved family of signal-modulating proteins 总被引:1,自引:0,他引:1
Takaki S Sauer K Iritani BM Chien S Ebihara Y Tsuji K Takatsu K Perlmutter RM 《Immunity》2000,13(5):599-609
Lnk is an SH2 domain-containing adaptor protein expressed preferentially in lymphocytes. To illuminate the importance of Lnk, we generated lnk(-/-) mice. Whereas T cell development was unaffected, pre-B and immature B cells accumulated in the spleens. In the bone marrow, B-lineage cells were proportionately increased, reflecting enhanced production of pro-B cells that resulted in part from hypersensitivity of precursors to SCF, the ligand for c-kit. Hence, Lnk ordinarily acts to regulate B cell production. Further characterization of lnk(-/-) mice also revealed that full-length Lnk is a 68 kDa protein containing a conserved proline-rich region and a PH domain. Lnk is a representative of a multigene adaptor protein family whose members act, by analogy with Lnk, to modulate intracellular signaling. 相似文献
102.
IL-1 is required for allergen-specific Th2 cell activation and the development of airway hypersensitivity response 总被引:1,自引:0,他引:1
Nakae S Komiyama Y Yokoyama H Nambu A Umeda M Iwase M Homma I Sudo K Horai R Asano M Iwakura Y 《International immunology》2003,15(4):483-490
IL-1 is a pro-inflammatory cytokine consisted of two molecular species, IL-1alpha and IL-1beta, and the IL-1 receptor antagonist (IL-1Ra) is a natural inhibitor of both molecules. Although it is suggested that IL-1 potentiates immune responses mediated by T(h)2 cells, the role of IL-1 in asthma still remains unclear. In this study, we demonstrate that the ovalbumin (OVA)-induced airway hypersensitivity response (AHR) in IL-1alpha/beta-deficient (IL-1alpha/beta(-/-)) mice was significantly reduced from the levels seen in wild-type mice, whereas the responses seen in IL-1Ra(-/-) mice were profoundly exacerbated, suggesting that IL-1 is required for T(h)2 cell activation during AHR. OVA-specific T cell proliferation, IL-4 and IL-5 production by T cells, and IgG1 and IgE production by B cells in IL-1alpha/beta(-/-) mice were markedly reduced compared with these responses in wild-type mice; such responses were enhanced in IL-1Ra(-/-) mice. Using IL-1alpha(-/-) and IL-1beta(-/-) mice, we determined that both IL-1alpha and IL-1beta are involved in this reaction. Both IgG1 and IgE levels were reduced in IL-1beta(-/-) mice, while only IgE levels were affected in IL-1alpha(-/-) mice, indicating a functional difference between IL-1alpha and IL-1beta. These observations indicate that IL-1 plays important roles in the development of AHR. 相似文献
103.
Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma 下载免费PDF全文
Kawikova I Paliwal V Szczepanik M Itakura A Fukui M Campos RA Geba GP Homer RJ Iliopoulou BP Pober JS Tsuji RF Askenase PW 《Immunology》2004,113(2):234-245
Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper‐reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1‐day immune cells. Responses are absent in 1‐day immune B‐cell‐deficient JH?/? mice and B‐1 B‐cell‐deficient xid male mice, as well as in recipients of 1‐day immune cells depleted of cells with the B‐1 cell phenotype (CD19+ B220+ CD5+). As B‐1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti‐hapten IgM‐producing cells in the spleen and lymph nodes of 1‐day immune wild‐type mice, but not in xid mice. Then, we passively immunized naive mice with anti‐hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor‐deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B‐1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization. 相似文献
104.
Shimakura Y Kawada H Ando K Sato T Nakamura Y Tsuji T Kato S Hotta T 《Stem cells (Dayton, Ohio)》2000,18(3):183-189
Human bone marrow (BM) or mobilized peripheral blood (mPB) CD34(+) cells have been shown to loose their stem cell quality during culture period more easily than those from cord blood (CB). We previously reported that human umbilical CB stem cells could effectively be expanded in the presence of human recombinant cytokines and a newly established murine bone marrow stromal cell line HESS-5. In this study we assessed the efficacy of this xenogeneic coculture system using human BM and mPB CD34(+) cells as materials. We measured the generation of CD34(+)CD38(-) cells and colony-forming units, and assessed severe-combined immunodeficient mouse-repopulating cell (SRC) activity using cells five days after serum-free cytokine-containing culture in the presence or the absence of a direct contact with HESS-5 cells. As compared with the stroma-free culture, the xenogeneic coculture was significantly superior on expansion of CD34(+)CD38(-) cells and colony-forming cells and on maintenance of SRC activity. The PKH26 study demonstrated that cell division was promoted faster in cells cocultured with HESS-5 cells than in cells cultured without HESS-5 cells. These results indicate that HESS-5 supports rapid generation of primitive progenitor cells (PPC) and maintains reconstituting ability of newly generated stem cells during ex vivo culture irrespective of the source of samples. This xenogeneic coculture system will be useful for ex vivo manipulation such as gene transduction to promote cell division and the generation of PPC and to prevent loss of stem cell quality. 相似文献
105.
Takiyama Y; Sakoe K; Soutome M; Namekawa M; Ogawa T; Nakano I; Igarashi S; Oyake M; Tanaka H; Tsuji S; Nishizawa M 《Human molecular genetics》1997,6(7):1063-1068
To investigate the mechanism of the meiotic instability of expanded CAG
repeats in the gene for Machado-Joseph disease (MJD1), we analyzed the CAG
repeat sizes of 1036 single sperm from six individuals with Machado- Joseph
disease (MJD). The segregation ratio between single sperm with an expanded
allele and those with a normal allele is significantly different (P
<0.0001) from the expected 1:1 segregation ratio, which demonstrates
segregation distortion of expanded alleles in male meiosis. In single sperm
from individuals with the [expanded (CAG)n- CGG]/[normal (CAG)n-GGG]
genotype, significantly greater instability of the CAG repeat was observed
compared with single sperm from individuals with the [expanded
(CAG)n-CGG]/[normal (CAG)n-CGG] genotype (F-test, P <0.001). These
findings in single sperm confirm non-Mendelian transmission of the MJD1
gene and the effect of the intragenic CGG/GGG polymorphism on the
intergenerational instability of the CAG repeats in the MJD1 gene, which
have been observed in clinical and genetic studies. Our results indicate
similarities and dissimilarities between MJD and Huntington's disease or
myotonic dystrophy in terms of the inter-allelic interaction, segregation
distortions and size distribution of trinucleotide repeats in mutant
alleles. Further study is required to determine whether there is a common
mechanism underlying the instability of the triplet repeats in 'triplet
repeat diseases'.
相似文献
106.
Zou Jian-Ping; Yamamoto Norihiko; Fujii Tetsuya; Takenaka Hiroshi; Kobayashi Michiko; Herrmann Steven H.; Wolf Stanley F.; Fujiwara Hiromi; Hamaoka Toshiyuki 《International immunology》1995,7(7):1135-1145
Unfractionated spleen cells taken from tumor-bearing mice 2weeks after tumor implantation contained tumor-primed T cellswhich produced cytokines including IL-2 and IFN- when culturedin vitro. With progressive tumor growth this initial lymphokine-producingcapacity decreased. Here, we investigated the ability of IL-12to (I) restore suppressed IFN- production, (II) cause tumorregression and (II) induce anti-tumor protective immunity. Additionof rIL-12 to spleen cell cultures from 4- to 10-week-old tumor-bearingmice resulted in a striking enhancement in the production ofIFN- compared with cultures of these cells in the absence ofrIL-12 or of normal spleen cells in the presence of rIL-12.Five I.p. injections of rIL-12 into mice bearing s.c. tumorsinduced complete tumor regression. This was found when rIL-12was given at early (1–2 weeks), intermediate (4–5weeks) or even late (7 weeks) stages of tumor growth. Furthermore,IL-12-treated mice which rejected the primary tumor exhibitedcomplete resistance to a rechallenge with the same tumor butdid not reject a second syngenetic tumor. Immunohistochemicalanalyses following IL-12 treatment revealed that CD4+ and CD8+T cells infiltrate the tumor. More importantly, IFN- mRNA expressionwas observed in fresh tumor masses from tumor-bearing mice receivingIL-12 treatment The importance of IFN- was further demonstratedby the observation that the systemic administration of anti-IFN-mAb prior to IL-12 treatment completely abrogated the anti-tumoreffect of IL-12. Thus, these results indicate that administrationof modest levels of rIL-12 to tumor-bearing mice results intumor regression through mechanisms involving reversal of suppressedIFN- production by anti-tumor T cells and the establishmentof a tumor-specific protective immune response. 相似文献
107.
Igarashi S; Takiyama Y; Cancel G; Rogaeva EA; Sasaki H; Wakisaka A; Zhou YX; Takano H; Endo K; Sanpei K; Oyake M; Tanaka H; Stevanin G; Abbas N; Durr A; Rogaev EI; Sherrington R; Tsuda T; Ikeda M; Cassa E; Nishizawa M; Benomar A; Julien J; Weissenbach J; Tsuji S 《Human molecular genetics》1996,5(7):923-932
Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative
disorder caused by unstable expansion of a CAG repeat in the MJD1 gene at
14q32.1. To identify elements affecting the intergenerational instability
of the CAG repeat, we investigated whether the CGG/GGG polymorphism at the
3' end of the CAG repeat affects intergenerational instability of the CAG
repeat. The [expanded (CAG)n-CGG]/[normal (CAG)n- GGG] haplotypes were
found to result in significantly greater instability of the CAG repeat
compared to the [expanded (CAG)n- CGG]/[normal (CAG)n-CGG] or [expanded
(CAG)nGGG]/[normal (CAG)n-GGG] haplotypes. Multiple stepwise logistic
regression analysis revealed that the relative risk for a large
intergenerational change in the number of CAG repeat units (< -2 or >
2) is 7.7-fold (95% CI: 2.5-23.9) higher in the case of paternal
transmission than in that of maternal transmission and 7.4-fold (95% CI:
2.4-23.3) higher in the case of transmission from a parent with the
[expanded (CAG)n-CGG]/[normal (CAG)n-GGG] haplotypes than in that of
transmission from a parent with the [expanded (CAG)n-CGG]/[normal
(CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal (CAG)n-GGG] haplotypes. The
combination of paternal transmission and the [expanded (CAG)n-CGG]/[normal
(CAG)n-GGG] haplotypes resulted in a 75.2-fold (95% CI: 9.0-625.0) increase
in the relative risk compared with that of maternal transmission and the
[expanded (CAG)n-CGG]/[normal (CAG)n-CGG] or [expanded (CAG)n- GGG]/[normal
(CAG)n-GGG] haplotypes. The results suggest that an inter- allelic
interaction is involved in the intergenerational instability of the
expanded CAG repeat.
相似文献
108.
A sensitive double antibody enzyme immunoassay for the quantitation of cyclic AMP and cyclic GMP is presented. Specific antisera to each nucleotide were raised in rabbits by immunization with succinyl cyclic nucleotide-human serum albumin conjugates. For competitive reaction, antibodies were incubated with a mixture of succinyl cyclic nucleotide labelled with beta-D-galactosidase and unlabelled succinylated standard or sample cyclic nucleotides. The antibody-bound enzyme-hapten was separated from free hapten by anti-rabbit IgG immobilized to a polystyrene ball. Activity of the enzyme on the solid phase was fluorometrically determined. The assay system made it possible to ascertain values as low as 5 fmole of cyclic AMP or cyclic GMP. Cyclic nucleotides in plasma could be accurately determined by this method without requiring a deproteinizing reagent as the first step of assay. 相似文献
109.
Gastric motility in patients with recurrent gastric ulcers. 总被引:3,自引:0,他引:3
Takeshi Kamiya Yuka Kobayashi Makoto Hirako Naoko Misu Toshihiro Nagao Michiko Hara Eriko Matsuhisa Takashi Ando Hiroshi Adachi Nagahiko Sakuma Genjiro Kimura 《Journal of Smooth Muscle Research》2002,38(1-2):1-9
The existence of abnormal gastric motility in gastric ulcer disease remains controversial. The aim of this study was to characterize gastric motility in patients with recurrent gastric ulcers. Studies were performed in 10 control subjects and in 24 patients with recurrent active gastric ulcer disease as diagnosed by gastrointestinal endoscopy. Gastric motility was evaluated by cutaneous electrogastrography (EGG) and by gastric semi-liquid meal emptying. The EGG was recorded before and after ingestion of a test meal containing 20 mg/kg of acetaminophen. Patients with a dominant EGG frequency of greater than 0.06 Hz were defined as tachygastria, while those with a frequency of less than 0.04 Hz were defined as bradygastria. A transient frequency decrease, called postprandial dip (PD), was identified visually. The degree of gastric emptying was determined from the serum acetaminophen concentration 45 minutes after the meal. Control subjects showed no irregularity in their dominant EGG frequency in tither fasting or postprandial states. PD was observed in 8 control subjects. In patients presenting with active gastric ulcers, abnormal patterns in the dominant EGG frequency (either as tachygastria or bradygastria) were observed in 14 of the 24 patients when fasting and in 15 of them in the postprandial state. After successful treatment, the number of patients with abnormal patterns in their dominant EGG frequency remained unchanged, while PD was observed in 11 patients. No significant difference was observed in the EGG power ratio as a result of successful treatment. Gastric emptying was significantly delayed compared with controls in both the active and healed stages. These findings suggest that abnormal gastric motility, including gastric electrical abnormalities and delayed gastric emptying, plays an important role in the pathophysiology of recurrent gastric ulcers. 相似文献
110.
An enzyme-linked immunosorbent assay for thyroxine in dried blood spotted on filter paper 总被引:2,自引:0,他引:2
We have developed a rapid and sensitive enzyme-linked immunosorbent assay (ELISA) for thyroxine (T4) in dried blood samples spotted on filter paper. The assay is carried out on microtiter plates without extraction or centrifugation steps. The detection limit of the assay is 5 pg/disc/well, equivalent to 1.25 micrograms/1 of whole blood or 2.5 micrograms/1 of serum. Intra- and inter-assay coefficients of variation for various T4 concentrations are 2.4-9.0% and 5.9-17.5% respectively. Correlation between the proposed ELISA method and the RIA is good (r = 0.900, n = 62, y(RIA) = 0.99x(ELISA) + 9.90). The ELISA method is useful for mass-screening of neonatal congenital hypothyroidism using dried blood samples on filter paper, is very simple and one person can assay more than 300 samples per day. 相似文献