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21.
Molecular determinants of human uveal melanoma invasion and metastasis 总被引:19,自引:0,他引:19
Seftor EA Meltzer PS Kirschmann DA Pe'er J Maniotis AJ Trent JM Folberg R Hendrix MJ 《Clinical & experimental metastasis》2002,19(3):233-246
The molecular analysis of cancer has benefited tremendously from the sequencing of the human genome integrated with the science
of bioinformatics. Microarray analysis technology has the potential to classify tumors based on the differential expression
of genes. In the current study, a collaborative, multidisciplinary approach was utilized to study the molecular determinants
of human uveal melanoma invasion and metastasis. Uveal melanoma is considered the most common primary intraocular cancer in
adults, resulting in the death of approximately 50% of patients affected. Unfortunately, at the time of diagnosis, many patients
already harbor microscopic metastases, thus underscoring a critical need to identify prognostic markers indicative of metastatic
potential. The investigative strategy consisted of isolating highly invasive vs. poorly invasive uveal melanoma cells from
a heterogeneous tumor derived from cells that had metastasized from the eye to the liver. The heterogeneous tissue explant
MUM-2 led to the derivation of two clonal cell lines: MUM-2B and MUM-2C. Further morphological and functional analyses revealed
that the MUM-2B cells were epithelioid, interconverted (expressing mesenchymal and epithelial phenotypes) highly invasive,
and demonstrated vasculogenic mimicry. The MUM-2C cells were spindle-like, expressed only a vimentin mesenchymal phenotype,
poorly invasive, and were incapable of vasculogenic mimicry. The molecular analysis of the MUM-2B vs. the MUM-2C clones resulted
in the differential expression of 210 known genes. Overall, the molecular signature of the MUM-2B cells resembled that of
multiple phenotypes – similar to a pluripotent, embryonic-like genotype. Validation of select genes that were upregulated
and down-regulated was conducted by semiquantitative RT-PCR measurement. This study provides a molecular profile that will
hopefully lead to the development of new molecular targets for therapeutic intervention and possible diagnostic markers to
predict the clinical outcome of patients with uveal melanoma.
This revised version was published online in July 2006 with corrections to the Cover Date. 相似文献
22.
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献
23.
Catt SL; Sakkas D; Bizzaro D; Bianchi PG; Maxwell WM; Evans G 《Molecular human reproduction》1997,3(9):821-825
Controlling the sex of offspring by the separation of X and Y
chromosome-bearing spermatozoa using flow cytometry has been reported as a
clinical technique aiding prevention of X-linked diseases. Although this
technique has resulted in several hundred normal births in animals and at
least one human birth, there is still concern over its genetic safety due
to the involvement of two potentially mutagenic agents: UV light and the
fluorochrome dye, Hoechst 33342 (H33342). Human spermatozoa, particularly
those considered abnormal, may be more likely to suffer DNA damage
following exposure to mutagenic agents, compared with other mammalian
species. The stability of normal fresh and decondensed human spermatozoa
were examined after exposure to a range of levels of UV and H33342
staining, using an assay that detects endogenous nicks in the DNA of
spermatozoa. The stability of abnormal and normal, fresh and frozen-thawed
human spermatozoa was examined following UV laser, H33342 staining and flow
cytometry treatments utilizing the same assay. There was an increase in the
presence of endogenous nicks when spermatozoa were decondensed compared
with fresh spermatozoa. There was no increase in the incidence of nicks in
any group of spermatozoa after UV and fluorochrome exposure compared with
controls without exposure.
相似文献
24.
Winberg JO; Hammami-Hauasli N; Nilssen O; Anton-Lamprecht I; Naylor SL; Kerbacher K; Zimmermann M; Krajci P; Gedde-Dahl T Jr; Bruckner-Tuderman L 《Human molecular genetics》1997,6(7):1125-1135
Dystrophic epidermolysis bullosa (EBD) is a clinically heterogeneous skin
disorder, characterized by abnormal anchoring fibrils (AF) and loss of
dermal-epidermal adherence. EBD has been linked to the COL7A1 gene at
chromosome 3p21 which encodes collagen VII, the major component of the AF.
Here we investigated two unrelated EBD families with different clinical
phenotypes and novel combinations of recessive and dominant COL7A1
mutations. Both families shared the same recessive heterozygous 14 bp
deletion at the exon-intron 115 boundary of the COL7A1 gene. The deletion
caused in-frame skipping of exon 115 and the elimination of 29 amino acid
residues from the pro-alpha1(VII) polypeptide chain. As a result,
procollagen VII was not converted to collagen VII and the C-terminal NC-2
propeptide which is normally removed from the procollagen VII prior to
formation of the anchoring fibrils was retained in the skin. All affected
individuals also carried missense mutations in exon 73 of COL7A1 which lead
to different glycine- to-arginine substitutions in the triple-helical
domain of collagen VII. Combination of the deletion mutation with a G2009R
substitution resulted in a mild phenotype. In contrast, combination of the
deletion with a G2043R substitution led to a severe phenotype. The G2043R
substitution was a de novo mutation which alone caused a mild phenotype.
Thus, different combinations of dominant and recessive COL7A1 mutations can
modulate disease activity of EBD and alter the clinical presentation of the
patients.
相似文献
25.
During the training phase, 96 subjects were given one of four types of relaxation instructions (single instructions, repeated instructions, relaxation training, no instructions) and in addition either did or did not receive frontal EMG biofeedback training. Results indicated that each of the instructions and biofeedback procedures were equally effective in reducing frontal EMG, but that none of these procedures had any effect on subjective anxiety or autonomic indices of arousal (pulse rate, skin temperature, and finger pulse volume). During the generalization/stress phase, subjects were threatened with electric shock and were told to apply the relaxation techniques they learned during the training phase even though no additional instructions and/ or biofeedback training would be provided. To assess the effectiveness of the shock manipulation, a no-threat control group was included. Results indicated that: a) the shock manipulation was effective in increasing arousal, b) previous instructions and/or biofeedback were equally effective in reducing frontal EMG levels, but that c) only relaxation training was consistently effective in reducing subjective and autonomic indices of arousal. These findings: a) suggest that in stressful situations, relaxation training may be more effective than either EMG biofeedback or simple relaxation instructions in producing a general relaxation effect as opposed to a specific EMG effect; and b) indicate the importance of assessing the effectiveness of relaxation procedures during stressful situations during which subjects’ levels of arousal are elevated above resting baseline levels. 相似文献
26.
Molecular cloning and sequence analysis of the gene encoding the major merozoite surface antigen of Plasmodium chabaudi chabaudi IP-PC1 总被引:1,自引:0,他引:1
W Deleersnijder D Hendrix N Bendahman J Hanegreefs L Brijs C Hamers-Casterman R Hamers 《Molecular and biochemical parasitology》1990,43(2):231-244
The complete nucleotide sequence of the gene encoding the precursor to the major merozoite surface antigens of Plasmodium chabaudi chabaudi strain IP-PC1 has been determined. A single open reading frame was detected, that coded for a protein of 199 kDa. The encoded protein (p199) contains putative signal and membrane anchor sequences and shows a clustering of Cys residues in the last 120 amino acids. Incompletely conserved tandem repeat oligopeptides are present at different positions in the molecule. P199 shows 69% overall homology to the analogous antigen in Plasmodium yoelii yoelii strain YM. The divergence between these antigens is largely confined to 4 areas where a number of insertions and/or deletions have occurred. All repeats occur in these divergent regions. The overall homology with both alleles of Plasmodium falciparum PMMSA is 33%. 相似文献
27.
0 引言 胃镜检查是上消化道疾病诊断的重要方法之一 .了解重复胃镜检查的原因及结果 ,有利于探讨疾病发生发展的基本规律 ,有利于发现诊断和治疗中存在的问题 ,从而提高对消化疾病的诊治水平 .1 材料和方法1.1 材料 随机抽检 1996 / 1998胃镜检查资料为调查对象7812例 ,其中行 2次以上胃镜检查者 937例 .调查内容包括性别、年龄、职业、主要症状和体征、病程、初步诊断、内镜检查时间、次数、内镜诊断、病理诊断、确诊时间 .1.2 方法 回顾性调查上述材料的临床特征 .列表统计研究对象一般情况的分布状况 ,计算各年龄段比例构成 ,各病… 相似文献
28.
29.
M Clerici A Sarin R L Coffman T A Wynn S P Blatt C W Hendrix S F Wolf G M Shearer P A Henkart 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(25):11811-11815
In vitro T-cell receptor-induced programmed cell death in both activated T cells from human immunodeficiency virus-seronegative (HIV-) donors and resting T cells from HIV+ donors was substantially influenced by cytokines. Addition of exogenous recombinant "type 1" lymphokines interferon gamma and interleukin 2 (IL-2), as well as the macrophage-produced IL-12, which favor cell-mediated T-cell responses, blocks both systems of T-lymphocyte programmed cell death. In contrast, the "type 2" lymphokines IL-4 and IL-10, which favor antibody responses, either had no effect or enhanced these systems of in vitro T-cell programmed cell death. A role for endogenously produced cytokines was suggested by the inhibition of T-cell receptor-mediated death by antibodies against IL-4 and IL-10 and its enhancement by anti-IL-12 in cultures containing monocytes. These results demonstrate that the functional properties of type 1 and type 2 cytokine classes may be further extended to include their effects on T-cell programmed cell death and their possible role in the pathogenesis of HIV infection. 相似文献
30.
S.L. Hendrix DO S.D. Piereson MD S.G. McNeeley MD 《American journal of obstetrics and gynecology》1995,172(6):1719-1725
Objective: Our purpose was to determine whether primary and preventive care is practiced by a university obstetrician-gynecologist group practice.Study design: A retrospective chart review spanning 2 years of four academic physicians' private practices was performed. A total of 335 patients were reviewed with 739 patient encounters and 1032 patient problems identified. The definition of a primary care physician according to The American College of Obstetricians and Gynecologists was used to standardize data collection and evaluation.Results: Obstetric complaints accounted for 27.7% of all visits, whereas 65.4% were for gynecologic problems. Almost 7% of all complaints were neither obstetric nor gynecologic, and of those 74.6% were primary care problems completely managed by the obstetrician-gynecologist. Only 19.7% of these were referred for management. More than 89% of all encounters () involved some element of primary care.Conclusion: This study provides evidence that the majority of health care provided by the obstetrician-gynecologists is primary care. 相似文献